Comprehensive Glycoscience: From Chemistry to Systems Biology

Front Cover
Comprehensive Glycoscience
Copyright
Editor Biographies
	Editor-in-Chief
	Volume Editors
List of Contributors for Volume 1
Preface
Contents of Volume 1
Permission Acknowledgement
1.01 Introduction to Comprehensive Glycoscience: The Good, the Better and What´s toCome
	1.01.1. Introduction
		1.01.1.1. Brief history of glycoscience
		1.01.1.2. What are carbohydrates/glycans and what do they looklike?
	1.01.2. Analysis of glycans
		1.01.2.1. High pH anion-exchange chromatography (HPAEC) and pulsed amperometric detection(PAD)
		1.01.2.2. Capillary electrophoresis(CE)
		1.01.2.3. Mass spectrometry
		1.01.2.4. NMR spectroscopy and molecular simulations
	1.01.3. Glycan synthesis
	1.01.4. Cellular glycan functions
		1.01.4.1. Glycan binding proteins
		1.01.4.2. Glycans in disease
	1.01.5. Summary and perspective
	Appendix
	References
	Relevant Websites
1.02 Bacterial Exopolysaccharides
	1.02.1. Introduction
	1.02.2. Composition, structure, and biosynthesis of exopolysaccharides: General aspects
	1.02.3. Exopolysaccharides in biofilms
	1.02.4. Exopolysaccharides of gram-negative bacteria
		1.02.4.1. Gammaproteobacteria-Enterobacteriales
			1.02.4.1.1. Enterobacteriaceae: Escherichia coli
			1.02.4.1.2. Enterobacteriaceae: Klebsiella and Raoultella
			1.02.4.1.3. Enterobacteriaceae: Other genera
			1.02.4.1.4. Other Enterobacteriales
		1.02.4.2. Other Gammaproteobacteria
			1.02.4.2.1. Vibrionaceae
			1.02.4.2.2. Pasteurellaceae
			1.02.4.2.3. Pseudomonadaceae
			1.02.4.2.4. Moraxellaceae: Acinetobacter baumannii
			1.02.4.2.5. Other Moraxellaceae
			1.02.4.2.6. Other families of Gammaproteobacteria
		1.02.4.3. Alphaproteobacteria
			1.02.4.3.1. Rhizobacteria and agrobacteria
			1.02.4.3.2. Sphingomonadaceae
			1.02.4.3.3. Acetobacteraceae
			1.02.4.3.4. Other Alphaproteobacteria
		1.02.4.4. Betaproteobacteria
			1.02.4.4.1. Burkholderiaceae
			1.02.4.4.2. Neisseriaceae
			1.02.4.4.3. Other Betaproteobacteria
		1.02.4.5. Epsilonproteobacteria
			1.02.4.5.1. Campylobacteraceae
		1.02.4.6. FCBgroup
			1.02.4.6.1. Bacteroidaceae
			1.02.4.6.2. Other families of FCBgroup
	1.02.5. Exopolysaccharides of gram-positive bacteria
		1.02.5.1. Bacilli-Lactobacillales: Pathogenic Streptococcus
			1.02.5.1.1. Streptococcus pneumoniae
			1.02.5.1.2. Streptococcus agalactiae
			1.02.5.1.3. Streptococcus suis
			1.02.5.1.4. Other pathogenic Streptococcus
		1.02.5.2. Bacilli-Lactobacillales: Lactic acid bacteria
			1.02.5.2.1. Food Streptococcaceae
			1.02.5.2.2. Lactobacillaceae and Leuconostocaceae
		1.02.5.3. Other bacilli
			1.02.5.3.1. Other Lactobacillales
			1.02.5.3.2. Bacillales
		1.02.5.4. Clostridia-Clostridiales
			1.02.5.4.1. Lachnospiraceae
			1.02.5.4.2. Clostridiaceae
		1.02.5.5. Actinobacteria: Food bacteria
			1.02.5.5.1. Bifidobacteriales
			1.02.5.5.2. Propionibacteriales
		1.02.5.6. Other Actinobacteria
			1.02.5.6.1. Corynebacteriales
			1.02.5.6.2. Micrococcales
			1.02.5.6.3. Streptomycetales
	1.02.6. Conclusions
	References
1.03 Fungal Polysaccharides
	1.03.1. General information offungi
		1.03.1.1. Taxonomy offungi
		1.03.1.2. Life cycle offungi
		1.03.1.3. Whole genome sequence (WGS) offungi
	1.03.2. Cell wall offungi
		1.03.2.1. Polysaccharide component
		1.03.2.2. Enzymes for synthesis
		1.03.2.3. Stress response
	1.03.3. Preparation of fungal polysaccharides
		1.03.3.1. General background
		1.03.3.2. Edible and medicinal mushrooms
		1.03.3.3. Yeasts andmolds
			1.03.3.3.1. Saccharomyces cerevisiae
			1.03.3.3.2. Candidaspp.
			1.03.3.3.3. Schizosaccharomyces (Schiz.)pombe
			1.03.3.3.4. Cryptococcusspp.
			1.03.3.3.5. Aspergillusspp.
			1.03.3.3.6. Mucorspp.
			1.03.3.3.7. α-Glucan
			1.03.3.3.8. Chitin and chitosan
			1.03.3.3.9. Higher-order structures of β-glucans
		1.03.3.4. Medical applications of β-glucan
			1.03.3.4.1. Early diagnosis of deep mycosis
			1.03.3.4.2. Innate immunity
			1.03.3.4.3. Pathological and immunopharmacological action
			1.03.3.4.4. Antibody
			1.03.3.4.5. Mucosal immune system
			1.03.3.4.6. Metabolism in thehost
		1.03.3.5. Medical applications of mannan
			1.03.3.5.1. Innate immunity
			1.03.3.5.2. Pathological and immunopharmacological action
			1.03.3.5.3. Acquired immunity of mannan (and galactomannan)
		1.03.3.6. Summary
	References
1.04 Seaweed Polysaccharides: Promising Molecules for Biotechnological Applications
	1.04.1. Introduction
	1.04.2. Agar
		1.04.2.1. Sources
		1.04.2.2. Chemical composition
		1.04.2.3. Extraction methods
		1.04.2.4. Physicochemical properties
		1.04.2.5. Applications
	1.04.3. Alginate
		1.04.3.1. Sources
		1.04.3.2. Chemical composition
		1.04.3.3. Extraction methods
		1.04.3.4. Physicochemical properties
		1.04.3.5. Applications
	1.04.4. Carrageenan
		1.04.4.1. Sources
		1.04.4.2. Chemical composition
		1.04.4.3. Extraction methods
		1.04.4.4. Physicochemical properties
		1.04.4.5. Applications
	1.04.5. Fucoidan
		1.04.5.1. Common sources
		1.04.5.2. Chemical composition
		1.04.5.3. Extraction methods
		1.04.5.4. Physicochemical properties
		1.04.5.5. Applications
	1.04.6. Ulvan
		1.04.6.1. Sources
		1.04.6.2. Chemical composition
		1.04.6.3. Extraction methods
		1.04.6.4. Physicochemical properties
		1.04.6.5. Applications
	1.04.7. Conclusion
	References
1.05 Common Cellular Glycans: Biosynthesis, Modifications and Functions in Cancer and Inflammation
	1.05.1. Introduction
		1.05.1.1. Introduction to glycans
		1.05.1.2. Types of normal glycosylation
			1.05.1.2.1. N-Glycosylation
			1.05.1.2.2. O-Glycosylation
			1.05.1.2.3. C-Glycosylation
			1.05.1.2.4. Glypiation
			1.05.1.2.5. Phosphoglycosylation
		1.05.1.3. Glycolipids
	1.05.2. Glycans and disease
		1.05.2.1. Congenital disorders of glycosylation
		1.05.2.2. Glycans and inflammation
			1.05.2.2.1. Glycans in microbe host interactions
			1.05.2.2.2. Glycans in viral infections
			1.05.2.2.3. Glycosylation of immunoglobulinG
			1.05.2.2.4. Binding of glycans with cell surface receptors and inflammation
				1.05.2.2.4.1. Siglecs
				1.05.2.2.4.2. Galectins
			1.05.2.2.5. Glycosylation of lymphocytes
				1.05.2.2.5.1. Bcells
				1.05.2.2.5.2. Tcells
		1.05.2.3. Glycans incancer
			1.05.2.3.1. N-glycosylation incancer
			1.05.2.3.2. O-glycosylation in cancers
			1.05.2.3.3. Sialyation incancer
			1.05.2.3.4. Fucosylation incancer
	1.05.3. Glycans as personalized medicine
		1.05.3.1. Biomarkers
			1.05.3.1.1. Biomarkers forcancer
			1.05.3.1.2. Biomarker for inflammation
		1.05.3.2. Detection of biomarkers
		1.05.3.3. Immune checkpoint blockade therapy
		1.05.3.4. Intravenous immunoglobulin (IVIG) therapy
	1.05.4. Conclusions and future directions
	References
1.06 C-Mannosyl Tryptophan: From Chemistry to Cell Biology
	1.06.1. Introduction
	1.06.2. Identification and measurement of C-mannosyl tryptophan(CMW)
	1.06.3. CMW-related compounds
	1.06.4. Biosynthesis of CMW in proteins
	1.06.5. Synthesis ofCMW
	1.06.6. Synthesis of CMW-containing peptides
	1.06.7. N-Mannosyl-tryptophan (NMW) synthesis
	1.06.8. Protein targets for C-mannosylation in thecell
	1.06.9. Identification of C-mannosyltransferases
	1.06.10. Functional significance of protein C-mannosylation in thecell
	1.06.11. Prospective functions of C-mannosylated peptide motifs in thecell
	1.06.12. C-Mannosylation in biology and medicine
		1.06.12.1. CMW as a biomarker of renal functions
		1.06.12.2. Protein C-mannosylation defects and diseases
		1.06.12.3. Protein C-mannosylation and CMW in metabolic disorders
		1.06.12.4. Protein C-mannosylation and CMW in cancer biology
	1.06.13. Others
	References
1.07 O-Fucosylation of Proteins
	1.07.1. Introduction
	1.07.2. Discovery of O-fucose modification on proteins
		1.07.2.1. O-Fucose on EGF repeats
		1.07.2.2. O-Fucose in other protein contexts includingTSRs
		1.07.2.3. O-Fucosylation of nuclear and cytoplasmic proteins
	1.07.3. Biosynthetic pathway for O-fucosylation of EGF repeats
		1.07.3.1. Protein O-fucosyltransferase 1 (POFUT1)
		1.07.3.2. Fucose-specific β3-GlcNAc transferases of the Fringe family
		1.07.3.3. Galactosyltransferase and sialyltransferases necessary to complete the O-fucose tetrasaccharide
	1.07.4. Biosynthetic pathway for O-fucosylation ofTSRs
		1.07.4.1. Protein O-fucosyltransferase 2 (POFUT2)
		1.07.4.2. Fucose-specific β3-glucosyltransferase
	1.07.5. Biological effects of EGF O-fucosylation
		1.07.5.1. Biological role of POFUT1 onNotch
		1.07.5.2. Biological role of Fringes onNotch
		1.07.5.3. Biological role of galactosyltransferases and sialyltransferases onNotch
		1.07.5.4. Role of O-fucose on other EGF repeat-containing proteins
			1.07.5.4.1. Role of O-fucose on urinary-type plasminogen activator
			1.07.5.4.2. Role of O-fucose on CRIPTO
			1.07.5.4.3. Role of O-fucose onagrin
			1.07.5.4.4. Role of O-fucose on Delta ligands
	1.07.6. Molecular mechanisms underlying the effects of O-fucosylation onNotch
		1.07.6.1. O-Fucose saccharides directly affect the interaction of Notch and ligands
		1.07.6.2. O-Fucosylation on different EGF repeats affects Notch signaling in differentways
		1.07.6.3. The role of O-fucose in folding and stability of EGF repeats and trafficking ofNotch
	1.07.7. Biological effects of TSR O-fucosylation
		1.07.7.1. Biological role of POFUT2
		1.07.7.2. Biological role of B3GLCT
	1.07.8. Molecular mechanisms underlying the effects of O-fucosylation onTSRs
	1.07.9. Conclusions and future directions
	References
1.08 Structure, Classification and Modification of Polysaccharides
	1.08.1. Classification
		1.08.1.1. Classification by the origin of polysaccharides
			1.08.1.1.1. Plant polysaccharides
			1.08.1.1.2. Animal polysaccharides
			1.08.1.1.3. Microbial polysaccharides
		1.08.1.2. Classification by structural character of polysaccharides
			1.08.1.2.1. Monosaccharide composition and glycosidic linkage
				1.08.1.2.1.1. Homopolysaccharide
				1.08.1.2.1.2. Heteropolysaccharide
			1.08.1.2.2. The differences of the molecular chains
				1.08.1.2.2.1. The types of molecular chains
				1.08.1.2.2.2. The sequence types of sugarunits
			1.08.1.2.3. Others
				1.08.1.2.3.1. Functional groups
				1.08.1.2.3.2. Functional properties
	1.08.2. Structural and conformational characterization of polysaccharides
		1.08.2.1. Structure characterization methods of polysaccharides
		1.08.2.2. Chemical structure of polysaccharides
			1.08.2.2.1. Plant polysaccharides
				1.08.2.2.1.1. Storage carbohydrates/starch
				1.08.2.2.1.2. Terrestrial plants polysaccharides
				1.08.2.2.1.3. Marine plant polysaccharides
			1.08.2.2.2. Animal polysaccharides
			1.08.2.2.3. Microbial polysaccharides
		1.08.2.3. Chain conformation
	1.08.3. Molecular modification
		1.08.3.1. Physical modification
			1.08.3.1.1. Ultrasonication degradation
			1.08.3.1.2. Microwave exposure
		1.08.3.2. Enzymatic modification
		1.08.3.3. Chemical modification
			1.08.3.3.1. Sulfated modification
			1.08.3.3.2. Carboxymethylation modification
			1.08.3.3.3. Acetylation modification
			1.08.3.3.4. Phosphorylation modification
			1.08.3.3.5. Selenization modification
			1.08.3.3.6. Acid/alkali degradation
	1.08.4. Conclusion
	Acknowledgment
	References
1.09 Overview of Cellulose Types and Applications
	1.09.1. Introduction
	1.09.2. Structure of cellulose
	1.09.3. Types of cellulose
		1.09.3.1. Cellulose nanocrystals
			1.09.3.1.1. Preparation methods of cellulose nanocrystals
			1.09.3.1.2. Properties of cellulose nanocrystals
			1.09.3.1.3. Applications of cellulose nanocrystals
		1.09.3.2. Bacterial cellulose
			1.09.3.2.1. Structure and properties
			1.09.3.2.2. Applications of bacterial cellulose
		1.09.3.3. Cellulose nanofibrils
			1.09.3.3.1. Preparation of cellulose nanofibrils
			1.09.3.3.2. Applications of cellulose nanofibrils
		1.09.3.4. Regenerated cellulose
			1.09.3.4.1. Preparation methods of regenerated cellulose
			1.09.3.4.2. Applications of regenerated cellulose
	1.09.4. Conclusion
	Acknowledgment
	References
1.10 Mucins: Structure and Function
	1.10.1. Introduction
	1.10.2. Biosynthesis of mucin-type O-glycans
	1.10.3. Mucins and O-glycan alterations in diseases
	1.10.4. Types of mucins
		1.10.4.1. Secreted mucins/gel-forming
			1.10.4.1.1. MUC2
			1.10.4.1.2. MUC5AC
			1.10.4.1.3. MUC5B
			1.10.4.1.4. MUC6
			1.10.4.1.5. MUC19
		1.10.4.2. Secreted mucins/non-gel-forming
			1.10.4.2.1. MUC7
			1.10.4.2.2. MUC8
			1.10.4.2.3. MUC9
		1.10.4.3. Membrane-bound mucins
			1.10.4.3.1. MUC1
			1.10.4.3.2. MUC3A
			1.10.4.3.3. MUC3B
			1.10.4.3.4. MUC4
			1.10.4.3.5. MUC12
			1.10.4.3.6. MUC13
			1.10.4.3.7. MUC14
			1.10.4.3.8. MUC15
			1.10.4.3.9. MUC16
			1.10.4.3.10. MUC17
			1.10.4.3.11. MUC20
			1.10.4.3.12. MUC21
			1.10.4.3.13. MUC22
	1.10.5. Summary
	References
1.11 High-pH Anion-Exchange Chromatography (HPAEC) and Pulsed Amperometric Detection (PAD) for Carbohydrate Analysis
	1.11.1. Introduction
	1.11.2. Technology overview
		1.11.2.1. High-pH anion-exchange chromatography (HPAEC) of carbohydrates
			1.11.2.1.1. Eluent considerations forHPAEC
			1.11.2.1.2. Gradient considerations
			1.11.2.1.3. The problem of carbonate
			1.11.2.1.4. Alkaline lability of carbohydrates inHPAEC
			1.11.2.1.5. Columns forHPAEC
		1.11.2.2. Pulsed amperometric detection/pulsed electrochemical detection
			1.11.2.2.1. Pulsed electrochemical detection of carbohydrates
			1.11.2.2.2. Recent developments in electrochemical carbohydrate detection
			1.11.2.2.3. Integrated pulsed amperometric detection (IPAD) of other species
			1.11.2.2.4. Selectivity, sensitivity, and dynamic range ofPAD
	1.11.3. Glycobiology applications
		1.11.3.1. Monosaccharide composition analysis
			1.11.3.1.1. Analysis of neutral and amino-monosaccharides
			1.11.3.1.2. Quantitative sialic acid analysis
			1.11.3.1.3. Analysis of other monosaccharides
			1.11.3.1.4. Eluent generation technology
		1.11.3.2. Oligosaccharide separations
			1.11.3.2.1. Release and analysis of N-linked glycoprotein oligosaccharides
			1.11.3.2.2. Release and analysis of O-linked glycoprotein oligosaccharides
			1.11.3.2.3. HPAEC/PAD analysis of other carbohydrates
		1.11.3.3. Preparative isolation by HPAEC (andPAD)
	1.11.4. (Bio)Pharmaceutical applications (and implications)
		1.11.4.1. HPAEC/PAD and the three ``Cs´´: Consistency, comparability and characterization
		1.11.4.2. Therapeutic glycoproteins, monoclonal antibodies, and glycoconjugate vaccines
		1.11.4.3. Interfacing HPAEC/PAD with mass spectrometry
	1.11.5. Summary
	Acknowledgment
	References
1.12 Capillary Electrophoresis
	1.12.1. Introduction
		1.12.1.1. Significance and overview
		1.12.1.2. Instrumentation
			1.12.1.2.1. Capillary electrophoresis instrumentation
			1.12.1.2.2. Microfluidics
	1.12.2. Analyses of free oligosaccharides
		1.12.2.1. Sample preparation
			1.12.2.1.1. Sample labeling
			1.12.2.1.2. Releasing N-glycans from glycoproteins
		1.12.2.2. Detector based identification
			1.12.2.2.1. Optical methods of detection
			1.12.2.2.2. Peak assignment with migration time standards
			1.12.2.2.3. Mass spectrometry
			1.12.2.2.4. Peak identification with lectin recognition
			1.12.2.2.5. Peak identification through exoglycosidase sequencing
		1.12.2.3. Separations of neutral, asialylated N-glycans
			1.12.2.3.1. Contributions of electrophoresis and electroosmosis in glycan separations
			1.12.2.3.2. Separation with gel additives
			1.12.2.3.3. Separations that incorporate secondary selectors as a pseudo-stationaryphase
			1.12.2.3.4. Separations that incorporate a stationaryphase
		1.12.2.4. Separations of anionic, sialylated oligosaccharides
			1.12.2.4.1. Separation challenges of sialylated glycans
			1.12.2.4.2. Separating sialylated glycans through chemical labeling
			1.12.2.4.3. Separating sialylated glycans with enzymes
	1.12.3. Glycosaminoglycans
		1.12.3.1. Overview
		1.12.3.2. Capillary electrophoresis-absorbance detection of glycosaminoglycans
		1.12.3.3. Capillary electrophoresis-mass spectrometry of glycosaminoglycans
		1.12.3.4. Capillary affinity electrophoresis of glycosaminoglycan-protein interactions
	1.12.4. Future directions
	Acknowledgment
	References
1.13 Modern Mass Spectrometry Techniques for Oligosaccharide Structure Determination: Logically Derived Sequence Tandem Mass Spe ...
	1.13.1. Introduction
	1.13.2. Experimental method and instrument
	1.13.3. Dissociation mechanisms of carbohydrates
		1.13.3.1. Dissociation mechanisms of sodium adducts
			1.13.3.1.1. Hexose monosaccharides
			1.13.3.1.2. Dehydration of hexoses at the reducing end of disaccharides and oligosaccharides
			1.13.3.1.3. Cross-ring dissociation of hexoses at the reducing end of disaccharides and oligosaccharides
			1.13.3.1.4. Glycosidic bond cleavage
		1.13.3.2. Dissociation mechanism of lithium adducts
			1.13.3.2.1. Hexose monosaccharides
			1.13.3.2.2. Hexoses at the reducing end of disaccharides and oligosaccharides
	1.13.4. Applications of LODES/MSn for determining the structure of oligosaccharides
		1.13.4.1. Sodium adducts
			1.13.4.1.1. LODES of hexose trisaccharides
				1.13.4.1.1.1. Type determination
				1.13.4.1.1.2. Linear trisaccharides
				1.13.4.1.1.3. Branched trisaccharides
			1.13.4.1.2. Applications to glucose trisaccharides
				1.13.4.1.2.1. Example 1 α-Glc-(16)-α-Glc-(14)-Glc
				1.13.4.1.2.2. Example 2 β-Glc-(14)-β-Glc-(13)-Glc
				1.13.4.1.2.3. Example 3 β-Glc-(12)-β-Glc-(12)-Glc
				1.13.4.1.2.4. Example 4 α-Glc-(16)-(α-Glc-(14))-Glc
				1.13.4.1.2.5. Example 5 β-Glc-(12)-(β-Glc-(13))-Glc
			1.13.4.1.3. LODES of hexose tetrasaccharides
			1.13.4.1.4. Applications to mannose tetrasaccharides
				1.13.4.1.4.1. Example 1 α-Man-(12)-α-Man-(13)-α-Man-(16)-Man
				1.13.4.1.4.2. Example 2 α-Man-(16)-(α-Man-(13))-α-Man-(16)-Man
				1.13.4.1.4.3. Example 3 α-Man-(12)-α-Man-(13)-(α-Man-(16))-Man
		1.13.4.2. Lithium adducts
			1.13.4.2.1. LODES of hexose trisaccharides
			1.13.4.2.2. Applications to hexose trisaccharides
	1.13.5. Conclusions and future perspectives
	Acknowledgment
	References
1.14 General NMR Spectroscopy of Carbohydrates and Conformational Analysis in Solution
	1.14.1. Introduction
	1.14.2. NMR spectroscopy of carbohydrates
		1.14.2.1. General aspects
		1.14.2.2. Chemical shifts
		1.14.2.3. Assignments of resonances in NMR spectra
		1.14.2.4. Sequence determination
	1.14.3. Conformational analysis in solution
		1.14.3.1. Degrees of freedom
		1.14.3.2. Experimental NMR observables
			1.14.3.2.1. 1H,1H cross-relaxation
			1.14.3.2.2. 13C auto-relaxation
			1.14.3.2.3. Indirect spin-spin couplings
			1.14.3.2.4. Residual dipolar couplings
			1.14.3.2.5. Miscellaneous
				1.14.3.2.5.1. Exchangeable protons
				1.14.3.2.5.2. Translational diffusion
		1.14.3.3. Molecular simulations
	1.14.4. Concluding remarks
	Acknowledgment
	References
1.15 Computational Modeling in Glycoscience
	1.15.1. Introduction
	1.15.2. Structural diversity and conformational challenges
	1.15.3. Computational concepts andtools
		1.15.3.1. From quantum chemistry to coarse-grained calculations
			1.15.3.1.1. The all atoms representation in molecular mechanics and molecular dynamics computations
			1.15.3.1.2. Molecular mechanics
			1.15.3.1.3. The all atom molecular dynamics
			1.15.3.1.4. Molecular dynamics: Coarse-grained simulations
		1.15.3.2. Heuristic approach
		1.15.3.3. Monte Carlomethod
		1.15.3.4. The genetic algorithm search
		1.15.3.5. Carbohydrate-water interactions
		1.15.3.6. Description of the available software and applications
	1.15.4. Glycans and glycoconjugates
		1.15.4.1. N- and O-linked glycans
			1.15.4.1.1. How core fucosylation affects the structure and ADCC function ofIgG1s
			1.15.4.1.2. Structure and dynamics of the HIV-1-Env glycanshield
		1.15.4.2. Structure, function and dynamics of glycolipids in the plasma membrane
	1.15.5. Polysaccharides
		1.15.5.1. Polysaccharides in solution
		1.15.5.2. Lipopolysaccharides in membranes
		1.15.5.3. Cellulose, nano celluloses and hemicelluloses
		1.15.5.4. Polysaccharide-protein interactions
	1.15.6. Carbohydrate-protein interactions
		1.15.6.1. Insights into enzymatic catalysis
		1.15.6.2. Glycosyltransferase atwork
		1.15.6.3. Glycosyl hydrolases
		1.15.6.4. Insight into protein-carbohydrate recognition
			1.15.6.4.1. Protein-Induced conformational distortion of glycan
			1.15.6.4.2. Docking carbohydrates on protein
		1.15.6.5. Insights into carbohydrate transport
		1.15.6.6. Glycosaminoglycans: TheGAGs
	1.15.7. Structural glycobioinformatics
	1.15.8. Conclusions
	References
1.16 Understanding the Structure and Function of Viral Glycosylation by Molecular Simulations: State-of-the-Art and Recent Case  ...
	1.16.1. Introduction
	1.16.2. Molecular simulations
		1.16.2.1. Carbohydrate force fields
			1.16.2.1.1. GLYCAM06
			1.16.2.1.2. CHARMM
		1.16.2.2. Conformational sampling
	1.16.3. Glycosylation of viral envelope glycoproteins
		1.16.3.1. The SARS-CoV-2S glycoprotein
		1.16.3.2. The influenza Ahemagglutinin(HA)
		1.16.3.3. The HIV-1 Env fusiontrimer
	1.16.4. Conclusions and perspectives
	Acknowledgment
	References
1.17 Tools and Methods to Study the Human Glycome
	1.17.1. Introduction
	1.17.2. Defining a glycome
		1.17.2.1. The human milk free glycan glycome
	1.17.3. Glycans from natural sources
		1.17.3.1. Generating glycans from glycoconjugates for glycomic analyzes
		1.17.3.2. Generating glycans from glycoconjugates for functional glycomic analyzes using glycan microarrays
		1.17.3.3. Quantities of biologically relevant glycans sufficient for functional glycomic analyzes are attainable
		1.17.3.4. N-Glycan production byORNG
		1.17.3.5. O-Glycan production byORNG
		1.17.3.6. Glycosphingolipid (GSL)-glycan production byORNG
		1.17.3.7. General applications ofORNG
		1.17.3.8. Use of ORNG for production of high-mannose type N-glycans
		1.17.3.9. Purification of tagged glycans with two dimensional HPLC and recyclingHPLC
		1.17.3.10. Unique by-products as mono-GlcNAc derivatives
	1.17.4. Potential for amplification of glycans
		1.17.4.1. Shotgun glycan microarrays as a discoverytool
	1.17.5. Next generation glycan microarrays using DNA-coded glycan library
		1.17.5.1. Glycan microarray using DNA-coded glycan library and next generation sequencing
		1.17.5.2. DNA coded glycan libraries for screeningcells
	1.17.6. Summary
	Acknowledgment
	References
1.18 Glycosciences.de: Databases and Tools to Support Research in Glycomics and Glycoproteomics
	1.18.1. Introduction
	1.18.2. Overview of Glycosciences.de Resources
		1.18.2.1. Databases
			1.18.2.1.1. Glycosciences.DB
			1.18.2.1.2. GlycoMapsDB
			1.18.2.1.3. GlycoCD
			1.18.2.1.4. MonosaccharideDB
		1.18.2.2. Tools
			1.18.2.2.1. 3D Structure Modeling
			1.18.2.2.2. Analysis of glycans in PDB entries
			1.18.2.2.3. NotationTools
			1.18.2.2.4. Tools to support experimental analysis of glycans
	1.18.3. Updates and New Developments
	1.18.4. Conclusion
	References
	Relevant Websites
1.19 Systems Glycobiology: Immunoglobulin G Glycans as Biomarkers and Functional Effectors in Aging and Diseases
	1.19.1. Introduction
	1.19.2. IgM, IgD, IgA, and IgE glycosylation
		1.19.2.1. ImmunoglobulinM
			1.19.2.1.1. IgM function
			1.19.2.1.2. IgM structure
			1.19.2.1.3. IgM glycosylation
		1.19.2.2. ImmunoglobulinD
			1.19.2.2.1. IgD glycosylation
		1.19.2.3. ImmunoglobulinA
			1.19.2.3.1. IgA structure
			1.19.2.3.2. IgA function
			1.19.2.3.3. IgA Fc glycosylation
			1.19.2.3.4. IgA hinge glycosylation
			1.19.2.3.5. IgA Fab glycosylation
			1.19.2.3.6. IgA joining chain and secretory component glycosylation
			1.19.2.3.7. Functions of IgA glycans
		1.19.2.4. ImmunoglobulinE
			1.19.2.4.1. IgE glycosylation
	1.19.3. Immunoglobulin Gstructure and function
		1.19.3.1. IgG structure
		1.19.3.2. IgG functions
		1.19.3.3. IgG subclasses
		1.19.3.4. Pathogens fight back againstIgG
	1.19.4. General aspects of immunoglobulin GN-glycosylation
		1.19.4.1. Structure of IgG N-glycans
		1.19.4.2. Positioning of Fc N-glycans
		1.19.4.3. Fc glycans affect IgG structure and function
		1.19.4.4. Asymmetrical Fc glycosylation
		1.19.4.5. Fab versus Fc glycan composition
		1.19.4.6. Fab glycans affect IgG structure and function
		1.19.4.7. Asymmetrical Fab glycosylation
		1.19.4.8. IgG3 O-glycans
	1.19.5. IgG glycosylation analytics
		1.19.5.1. Lectins
		1.19.5.2. Advanced analyticaltools
		1.19.5.3. Ultra-high-performance liquid chromatography (UHPLC) and capillary gel electrophoresis with laser-induced fluor ...
		1.19.5.4. MS-based methods
		1.19.5.5. Data interpretation
	1.19.6. Intricacy of IgG glycosylation regulation
		1.19.6.1. Extreme complexity of IgG glycome
		1.19.6.2. Inter-individual variation of IgG glycome
		1.19.6.3. Intra-individual variation of IgG glycome
		1.19.6.4. IgG glycosylation is affected by IgG amino acid sequence
		1.19.6.5. IgG glycosylation is influenced by activity of glycosyltransferases
		1.19.6.6. IgG glycosylation is influenced bygenes
		1.19.6.7. IgG glycosylation is influenced by environment
		1.19.6.8. Integration of all regulatory determinants at the level of IgG glycan biosynthesis
		1.19.6.9. Open questions
	1.19.7. Glycan composition modulates IgG effector functions
		1.19.7.1. Fc fucosylation
		1.19.7.2. Fc bisecting GlcNAc
		1.19.7.3. Fc galactosylation
			1.19.7.3.1. Type IFcγRs and complement
			1.19.7.3.2. FcRn
			1.19.7.3.3. Fc structure
		1.19.7.4. Fc sialylation
			1.19.7.4.1. Fc structure
			1.19.7.4.2. Type IFcγRs
			1.19.7.4.3. Type II FcRs and IVIg mode of action
			1.19.7.4.4. ComplementC1q
		1.19.7.5. Fab glycosylation
			1.19.7.5.1. Antigen binding
			1.19.7.5.2. Immune complex formation
			1.19.7.5.3. Aggregation and precipitation
			1.19.7.5.4. IVIg mode of action
	1.19.8. Changes in IgG N-glycosylation associated with physiological states
		1.19.8.1. Aging
			1.19.8.1.1. IgG galactosylation
			1.19.8.1.2. Inflammaging
			1.19.8.1.3. IgG sialylation
			1.19.8.1.4. IgG bisection
			1.19.8.1.5. IgG core fucosylation
		1.19.8.2. Sex hormones
			1.19.8.2.1. Sex
			1.19.8.2.2. Pregnancy and menstrualcycle
			1.19.8.2.3. Interventional studies
	1.19.9. Changes in IgG N-glycosylation associated with diseases
		1.19.9.1. Autoimmune and alloimmune diseases
		1.19.9.2. Malignant diseases
		1.19.9.3. Infectious diseases
		1.19.9.4. Cardiometabolic diseases
	1.19.10. IgG as a biomarker of biologicalage
		1.19.10.1. Biologicalage
		1.19.10.2. Biological age predictors
		1.19.10.3. Telomere length
		1.19.10.4. Epigeneticage
		1.19.10.5. Glycanage
		1.19.10.6. Composite biomarkers of biologicalage
	1.19.11. Future of IgG glycosylation
		1.19.11.1. Methodology
		1.19.11.2. Animal models
		1.19.11.3. Regulation and functionality
		1.19.11.4. Personalized medicine - Disease prediction and diagnosis, patient stratification, monitoring of disease progre ...
		1.19.11.5. Glycoengineering of therapeutic monoclonal antibodies
		1.19.11.6. Tailoring IVIg glycosylation
		1.19.11.7. Therapeutic administration of enzymes modulating endogenous IgG glycosylation
		1.19.11.8. Optimization of vaccination protocols aiming at elicitation of targeted IgG glycoforms
		1.19.11.9. The future
	1.19.12. Conclusions
	Funding
	References
1.20 Glycans of the Pathogenic Yeast Cryptococcus neoformans and Related Opportunities for Therapeutic Advances
	1.20.1. Introduction
		1.20.1.1. Major features of the organism
		1.20.1.2. Overview of pathogenesis and disease
		1.20.1.3. Current antifungal compounds
		1.20.1.4. Current lack of vaccines in clinicaluse
		1.20.1.5. Goals and organization of this article
			1.20.1.5.1. Goals
			1.20.1.5.2. Organization
	1.20.2. Protein-linked glycans
		1.20.2.1. Structure and synthesis of protein-linked glycans
			1.20.2.1.1. N-linked glycosylation
			1.20.2.1.2. O-linked glycosylation
			1.20.2.1.3. GPI anchor synthesis
		1.20.2.2. Roles in infection: Protein-linked glycans
		1.20.2.3. Therapeutic strategies related to GPI anchor synthesis
	1.20.3. Glycolipids
		1.20.3.1. Glycosphingolipids
			1.20.3.1.1. Acidic GSL synthesis
			1.20.3.1.2. Neutral GSL synthesis
		1.20.3.2. Roles in infection: Glycosphingolipids
		1.20.3.3. Therapeutic strategies related to glycosphingolipids
			1.20.3.3.1. Biosynthetic enzymes
			1.20.3.3.2. GSLs in the plasma membrane
			1.20.3.3.3. Immunotherapeutic strategies
	1.20.4. Cell wall glycans
		1.20.4.1. Structure and synthesis of the cryptococcal cellwall
			1.20.4.1.1. Glucans
			1.20.4.1.2. Chitin and chitosan
			1.20.4.1.3. Cell wall associated glycoproteins
			1.20.4.1.4. Major regulators of cell wall integrity
		1.20.4.2. Roles in infection: Cellwall
		1.20.4.3. Therapeutic strategies related to the cellwall
			1.20.4.3.1. Targeting cell wall glycan synthesis
			1.20.4.3.2. Cell wall related vaccine strategies
	1.20.5. Capsule
		1.20.5.1. Structure, synthesis, and assembly of capsule
			1.20.5.1.1. Regulation of capsule synthesis
			1.20.5.1.2. Capsule polysaccharide synthesis
			1.20.5.1.3. Capsule polysaccharide secretion and assembly
		1.20.5.2. Roles in infection: Capsule
		1.20.5.3. Therapeutic strategies related to capsule
	1.20.6. Perspectives and future directions
		1.20.6.1. Promising drug targets
			1.20.6.1.1. Targets unique to fungi and/orCn
			1.20.6.1.2. Druggable targets despite functional overlap
		1.20.6.2. Promising vaccines
		1.20.6.3. Relevance of glycobiology to combating cryptococcosis
	Acknowledgment
	References
1.21 Glycoinformatics Resources Integrated Through the GlySpace Alliance
	1.21.1. Introduction
	1.21.2. Glycoinformatics challenges
	1.21.3. The GlySpace Alliance approach
		1.21.3.1. Data integration
		1.21.3.2. The GlyCosmos collection
		1.21.3.3. The GlyGen collection
		1.21.3.4. The glycomicsExPASy collection
	1.21.4. License and data access
	1.21.5. Conclusion
	References
Back Cover
9780128222447_WEB02
	Front Cover
	Comprehensive Glycoscience
	Copyright
	Editor Biographies
		Editor-in-Chief
		Volume Editors
	List of Contributors for Volume 2
	Preface
	Contents of Volume 2
	Permission Acknowledgement
	2.01 Strategies in Oligosaccharide Synthesis
		2.01.1. Introduction and the linear approach to oligosaccharide synthesis
		2.01.2. Approaches of differential donor activation
			2.01.2.1. Active-latent approach
			2.01.2.2. Selective activation and orthogonal glycosylation
			2.01.2.3. Armed-disarmed chemoselective glycosylation strategy
			2.01.2.4. Hydrogen bond mediated aglycon delivery(HAD)
			2.01.2.5. Intramolecular aglycon delivery
			2.01.2.6. Auxiliaries
			2.01.2.7. Preactivation
		2.01.3. Iterative strategies
		2.01.4. Regioselective glycosylations
		2.01.5. Modular and convergent synthesis
		2.01.6. Chemoenzymatic synthesis
		2.01.7. Automated synthesis
		2.01.8. Conclusions and outlook
		References
	2.02 The Oxocarbenium Ion Intermediate
		2.02.1. Introduction
		2.02.2. Lifetime of glycosyl oxocarbeniumions
			2.02.2.1. Free glycosyl cations
			2.02.2.2. Protected glycosyl cations
		2.02.3. Indirect methods that have provided evidence for the existence of glycosyl cations
			2.02.3.1. KIE measurements
			2.02.3.2. Cation clock reactions
			2.02.3.3. Computation
		2.02.4. Spectroscopic characterization of glycosyl cations
			2.02.4.1. The cation poolmethod
			2.02.4.2. Combining superacids and low temperatureNMR
			2.02.4.3. Combining tandem mass spectrometry and IR ion spectroscopy
		2.02.5. Stability of glycosyl cations
			2.02.5.1. Stability of oxocarbeniumions
			2.02.5.2. Impact of the CO bonds on the glycosyl cation stability
				2.02.5.2.1. Computation studies
				2.02.5.2.2. Study of the acidic hydrolysis of glycosides
				2.02.5.2.3. Study of the spontaneous hydrolysis of glycosides
				2.02.5.2.4. Study of the relative reactivity of glycosyl donors
				2.02.5.2.5. Piperidinium ions as models
				2.02.5.2.6. Mass spectrometry
		2.02.6. The impact of glycosyl cation conformers on facial selectivity
			2.02.6.1. Study of the impact of individual and multiple CO bonds on the nucleophilic attack of pyranosyl oxocarbeniumions
			2.02.6.2. Study of polysubstituted dioxocarbenium ions as glycosyl cation surrogates
			2.02.6.3. Glycosylations operating with stereoselective nucleophilic attack of glycosyl oxocarbeniumions
		2.02.7. Furanoses
			2.02.7.1. Stability
			2.02.7.2. Facial selectivity
		2.02.8. Conclusion
		References
	2.03 Stereoelectronic Effects in Glycosylation Reactions
		2.03.1. Introduction
		2.03.2. Glycosyl donor: Reactivity
		2.03.3. Glycosyl cations: Stability, selectivity andshape
		2.03.4. Glycosyl cations: Experimental observations
		2.03.5. Glycosyl cations: Product-forming reactive intermediates
		2.03.6. Glycosyl cations: (Remote-)participation-assisted mechanistic pathways
		2.03.7. Glycosyl acceptor: Reactivity
		2.03.8. Glycosyl acceptor: Steric and conformational effects
		2.03.9. Conclusion
		Acknowledgment
		References
	2.04 Methods for O-Glycoside Synthesis
		2.04.1. Introduction
		2.04.2. Historical background of O-glycosylations
		2.04.3. Stereochemical aspect of O-glycosylations
		2.04.4. Glycosylations by nucleophilic substitution at the anomeric carbon atom of the glycosyldonor
			2.04.4.1. Hemiacetal donors
				2.04.4.1.1. Direct conversion of hemiacetals to O-glycosides (Table2)
				2.04.4.1.2. Insitu activation of hemiacetals (Table3)
					2.04.4.1.2.1. Activation via glycosyl halides (Fig.4)
					2.04.4.1.2.2. Activation via glycosyl sulfonates (Fig.5)
					2.04.4.1.2.3. Activation via glycosyl O-phosphonium intermediate (Fig.6)
					2.04.4.1.2.4. Activation via glycosyl O-sulfonium intermediates (Fig.7)
					2.04.4.1.2.5. Activation of hemiacetals with Lewisacids
					2.04.4.1.2.6. Miscellaneous activation methods for hemiacetals
			2.04.4.2. Glycosyl halides
				2.04.4.2.1. Glycosyl bromides and chlorides as donors (Table4)
				2.04.4.2.2. Glycosyl iodides as glycosyl donors (Table5)
				2.04.4.2.3. Glycosyl fluorides as glycosyl donors (Table6)
			2.04.4.3. Anomeric sulfur derivatives
				2.04.4.3.1. Alkyl and homoaryl thioglycosides (Table7)
				2.04.4.3.2. Heteroaryl thioglycosides (S-imidates) (Table8)
				2.04.4.3.3. Glycosyl sulfoxides and sulfones (Table9)
				2.04.4.3.4. Miscellaneous sulfur derivatives (Table10)
			2.04.4.4. Seleno and telluro derivatives (Table11)
			2.04.4.5. Glycosyl O-imidates
				2.04.4.5.1. Acetimidates and trichloroacetimidates (Table12)
				2.04.4.5.2. Trifluoroacetimidates and N-substituted trifluoro-imidates (Table13)
				2.04.4.5.3. Miscellaneous imidates (Table14. The structures of the various leaving groups are shown in Scheme 11)
			2.04.4.6. Glycosyl esters (Table15)
				2.04.4.6.1. Glycosylation with glycosyl esters via alkyne activation (Table15)
			2.04.4.7. O-glycosides
				2.04.4.7.1. Pentenyl glycosides (Table16)
				2.04.4.7.2. Vinyl glycosides (Table17)
				2.04.4.7.3. Alkynyl glycosides (Table18)
				2.04.4.7.4. Aryl and heteroaryl glycosides (Table19)
				2.04.4.7.5. Miscellaneous O-glycosides as glycosyl donors (Table20)
			2.04.4.8. Phosphorous derivatives
				2.04.4.8.1. Glycosyl phosphites (Table21)
				2.04.4.8.2. Glycosyl phosphates (Table22)
				2.04.4.8.3. Miscellaneous phosphorous derivatives (Table23. Structures are summarized in Fig.11)
			2.04.4.9. Glycosyl carbonates, carbamates and related derivatives (Table24. Structures of the leaving groups are collecte ...
			2.04.4.10. 1-O-Silyl glycosides as glycosyl donors (Table25)
			2.04.4.11. Orthoester donors (Table26)
			2.04.4.12. Oxazolines as glycosyl donors (Table27)
			2.04.4.13. Anhydrosugars as glycosyl donors (Table28)
			2.04.4.14. Anomeric N-derivatives as glycosyl donors (Table29)
			2.04.4.15. Sulfonates as glycosyl donors (Table30)
			2.04.4.16. 1,2 Cyclopropyl derivatives as glycosyl donors (Table31)
		2.04.5. Glycosylations by nucleophilic substitution at a carbon atom of the glycosyl acceptor (Table32)
		2.04.6. Glycosylations by addition
			2.04.6.1. 1,2-Addition to glycals (Table33)
			2.04.6.2. 2-Nitroglycals as glycosyl donors (Table34)
			2.04.6.3. Ferrier rearrangement of glycals (Table35)
		2.04.7. Miscellaneous glycosylation methods
		2.04.8. Summary
		References
	2.05 Synthesis of C- and S-Glycosides
		2.05.1. Introduction
			2.05.1.1. C-glycosides of biological relevance
			2.05.1.2. S-glycosides of biological relevance
		2.05.2. Procedures of C-glycosidation
			2.05.2.1. Reaction of glycosyl halides with organometallic reagents and carbanions
			2.05.2.2. C-glycosylation via glyconolactones
			2.05.2.3. C-glycosylation involving Lewis acid-catalyzed formation of oxoniumions
				2.05.2.3.1. Synthesis of 2-deoxy-C-glycosides
			2.05.2.4. C-glycosylation via olefination-cyclization
				2.05.2.4.1. C-glycosylation using stabilized ylides
				2.05.2.4.2. C-glycosylation using nonstabilized ylides
			2.05.2.5. C-glycosides by cyclization of diols and derivatives
			2.05.2.6. C-glycosylation of glycals
				2.05.2.6.1. Acid-catalyzed addition of carbon nucleophiles to glycals
				2.05.2.6.2. Transition metal-catalyzed addition of carbon nucleophiles to glycals
				2.05.2.6.3. Addition of carbon nucleophiles to glycals via 1,2-episulfonium intermediates
			2.05.2.7. C-glycosylation via 1,2-anhydrosugars
			2.05.2.8. C-glycosylation via glycosyl radicals
			2.05.2.9. C-glycosylation via glycosyl anions
			2.05.2.10. C-glycosylation via Ramberg-Backlund reaction
			2.05.2.11. Toward enzymatic C-glycosylation: Abiotechnological approach
		2.05.3. Procedures of S-glycosylation
			2.05.3.1. S-glycosylation by acid-promoted displacement at the anomeric center of glycosyl donors
			2.05.3.2. S-glycosylation via SN2 reaction of 1-thiosugar donors with activated acceptors
			2.05.3.3. S-glycosylation via SN2 reaction of thiolate anions on glycosyl halides
			2.05.3.4. S-glycosylation via Michael addition of 1-thiosugars to unsaturated acceptors
			2.05.3.5. Enzymatic S-glycosylation: The use of thioglycoligases
			2.05.3.6. Synthetic applications of S-glycosides
				2.05.3.6.1. Thioglycosides as glycosyl donors
				2.05.3.6.2. Toward the synthesis of glycoproteins: Synthesis of S-linked glycoconjugates
		2.05.4. Conclusions
		References
	2.06 Synthesis of Uronic Acid Containing Oligosaccharides
		2.06.1. Introduction
			2.06.2. General strategies
		2.06.3. Glycosaminoglycans(GAGs)
			2.06.3.1. Hyaluronan
			2.06.3.2. Heparin (HP) and heparan sulfate(HS)
			2.06.3.3. Chondroitin sulfate (CS) and dermatan sulfate(DS)
		2.06.4. Bacterial polysaccharides
			2.06.4.1. Oligosaccharides containing glucuronicacids
			2.06.4.2. Oligosaccharides containing galacturonicacid
			2.06.4.3. Oligosaccharides containing mannuronicacid
			2.06.4.4. Oligosaccharides containing other uronicacids
		2.06.5. Pectin
		2.06.6. Conclusion
		References
	2.07 Synthesis of Glycosides of Sialic Acid
		2.07.1. Introduction
		2.07.2. Chemical synthesis of O-sialosides
			2.07.2.1. Leaving groups
				2.07.2.1.1. Sialyl halides
				2.07.2.1.2. 2-Thio derivatives
				2.07.2.1.3. 2-O-Derivatives
			2.07.2.2. Positional modifications
				2.07.2.2.1. Modifications at C-1
				2.07.2.2.2. Modifications at C-3
					2.07.2.2.2.1. 3-Bromo- and 3-O-auxiliaries
					2.07.2.2.2.2. 3-Thio and 3-seleno auxiliaries
				2.07.2.2.3. O-Modifications
				2.07.2.2.4. Modifications at C-5
					2.07.2.2.4.1. N-Acetylacetamido
					2.07.2.2.4.2. Azido
					2.07.2.2.4.3. Trifluoroacetamido
					2.07.2.2.4.4. N-Trichloroethoxycarbonyl(NTroc)
					2.07.2.2.4.5. N-Phthalimido derivatives
					2.07.2.2.4.6. Isothiocyanate derivatives
				2.07.2.2.5. Cyclic protecting groups
		2.07.3. NMR-based assignment of anomeric configurations
		2.07.4. Synthesis of C-and S-glycosides
			2.07.4.1. C-Linked oligosaccharides
			2.07.4.2. S-Linked oligosaccharides
		2.07.5. Conclusions
		References
	2.08 Glycosylation With Furanosides
		2.08.1. Introduction
		2.08.2. Formation of furanosyl donors
			2.08.2.1. Fischer glycosylation and anomeric alkylation
			2.08.2.2. Dithioacetal cyclization
			2.08.2.3. High temperature acylation
			2.08.2.4. Per-silylation
			2.08.2.5. Lactone reduction
			2.08.2.6. Glycal ozonolysis
			2.08.2.7. Borate complexes
			2.08.2.8. Pyranoside-into-furanoside (PIF) rearrangement
			2.08.2.9. Ring contraction of thiopyranosides to thiofuranosides
		2.08.3. Glycosylations with furanosyl donors
			2.08.3.1. Synthesis of 1,2-trans-furanosides
			2.08.3.2. Synthesis of 1,2-cis-furanosides
				2.08.3.2.1. Use of conformationally-flexible donors
				2.08.3.2.2. Oxidation-reduction of C-2 glycosides
				2.08.3.2.3. Intramolecular aglycone delivery glycosylations
				2.08.3.2.4. Hydrogen-bond mediated aglycone delivery glycosylations
				2.08.3.2.5. Catalyst-controlled glycosylations
				2.08.3.2.6. Use of conformationally-restricted donors
		2.08.4. Conclusions
		References
	2.09 Synthesis of 2-Deoxyglycosides
		2.09.1. Introduction
		2.09.2. Types of glycosylations
			2.09.2.1. Addition to glycals
			2.09.2.2. Indirect synthesis with prosthetic groups
			2.09.2.3. Direct synthesis with glycosyl halides
			2.09.2.4. Direct synthesis with protecting group strategies
			2.09.2.5. Direct synthesis with glycosyl esters
			2.09.2.6. Direct synthesis with anionic donors
			2.09.2.7. Direct synthesis with glycosyl modulators
				2.09.2.7.1. Imidinium modulators
				2.09.2.7.2. Sulfonate modulators
			2.09.2.8. Direct synthesis with thioglycosides
			2.09.2.9. de novo Synthesis
		2.09.3. Conclusion
		References
	2.10 Electrochemical Activation of Glycosyl Donors
		2.10.1. Introduction
		2.10.2. Electrochemical oxidation of aryl glycosides (XO)
		2.10.3. Electrochemical oxidation of thioglycosides (XS)
		2.10.4. Electrochemical oxidation of selenoglycosides (XSe)
		2.10.5. Electrochemical oxidation of telluroglycosides (XTe)
		2.10.6. Electrochemical oxidative activation of glycosyl orthoester
		2.10.7. Electrochemical reduction of glycosyl bromides
		2.10.8. Summary
		References
	2.11 Photochemical Glycosylation
		2.11.1. Introduction
		2.11.2. Photochemistry basics
		2.11.3. C-Glycosylation involving anomeric radical intermediates
		2.11.4. Photochemical glycosylation proceeding via carbene and nitrene intermediates
		2.11.5. O-Glycosylation proceeding via electron-transfer or energy-transfer processes
			2.11.5.1. O-glycoside donors
			2.11.5.2. S-glycoside donors
			2.11.5.3. Se-glycoside donors
			2.11.5.4. Glycals
		2.11.6. Photoacid approaches to O-glycosylation
		2.11.7. Concluding remarks
		References
	2.12 1,2-cis O-Glycosylation Methods
		2.12.1. Introduction
		2.12.2. Earlier methods using glycosyl halides
		2.12.3. Molecular clamp approaches
		2.12.4. Intramolecular aglycon delivery(IAD)
			2.12.4.1. IAD using ketal-type tethers
			2.12.4.2. IAD using acetal-type tethers
		2.12.5. Leaving group-based approaches
		2.12.6. Hydrogen-bonding aglycon delivery(HAD)
		2.12.7. Boron-mediated aglycon delivery(BMAD)
			2.12.7.1. BMAD using organoboronicacids
			2.12.7.2. BMAD using organoborinicacids
		2.12.8. Neighboring group-based approaches
			2.12.8.1. Glycosylations using the electron-withdrawing effect of a neighboringgroup
			2.12.8.2. Glycosylations using neighboring group participation
		2.12.9. Remote group-based approaches
			2.12.9.1. Glycosylations using the directing effect of a potentially participatinggroup
			2.12.9.2. Glycosylations using the steric effect of a remote protectinggroup
		2.12.10. Conformationally-restrained glycosyl donor-based approaches
		2.12.11. Anomeric O-alkylations
		2.12.12. Organocatalyzed glycosylation approaches
		2.12.13. Other approaches
			2.12.13.1. Glycosylations using N-substituted-benzylidene glycosyl donors
			2.12.13.2. Amide/TBAI/phosphine oxide-modulated methods
		2.12.14. Concluding remarks
		References
	2.13 Glycosylation Through Intramolecular Aglycon Delivery
		2.13.1. Introduction
		2.13.2. Intramolecular aglycon delivery
			2.13.2.1. Development of IAD: The use of specific tethers
				2.13.2.1.1. Inception of IAD: Hindsgaul\'s Tebbe/mixed acetal tethering
				2.13.2.1.2. Stork\'s silaketal tethering
				2.13.2.1.3. Extensions and applications of these two original approaches
			2.13.2.2. The use of common alcohol protecting groups as latent tetheringsites
				2.13.2.2.1. Ogawa/Ito PMB approach
				2.13.2.2.2. Fairbanks\'s allyl ether and related approaches
				2.13.2.2.3. Ito\'s NAP ether approach
			2.13.2.3. Applications
				2.13.2.3.1. Synthesis of N-glycans
				2.13.2.3.2. Applications to furanosides
				2.13.2.3.3. Applications to other 1,2-cis linkages
				2.13.2.3.4. Iterative-IAD in oligosaccharide synthesis
		2.13.3. Summary and outlook
		References
	2.14 De Novo Synthesis of Oligosaccharides Via Metal Catalysis
		2.14.1. Introduction
		2.14.2. Metal glycosylation
			2.14.2.1. Gold(I)/(III)-catalyzed glycosylation
			2.14.2.2. Nickel(II)-catalyzed glycosylation
			2.14.2.3. Ferrier-rearrangement glycosylation vs. alcoholysis
			2.14.2.4. Ruthenium-catalyzed glycosylation/Ferrier-rearrangement
			2.14.2.5. Gold(III)-catalyzed glycosylation/Ferrier-rearrangement
			2.14.2.6. Rhenium-catalyzed glycosylation
			2.14.2.7. Photo-redox glycosylation
			2.14.2.8. Ruthenium/Iridium-catalyzed photo-glycosylation
		2.14.3. Pd(0)-Catalyzed glycosylation
			2.14.3.1. Achmatowicz approach to Pd-pyranone glycosyl donors
			2.14.3.2. Stereodivergent synthesis of Pd-glycosyl-donors
		2.14.4. Synthesis of unnatural oligosaccharides
			2.14.4.1. Synthesis of highly branched (14), (16)-heptasaccharides
		2.14.5. Application to natural products
			2.14.5.1. Synthesis of SL0101
			2.14.5.2. Synthesis of enones for Pd-cyclitolizations
			2.14.5.3. Synthesis of 5a-carba-sugar SL0101 analogs using the Pd-cyclitolizations
			2.14.5.4. Synthesis of Cleistriosides and Cleistetrosides family
			2.14.5.5. Synthesis of Anthrax tetrasaccharide
			2.14.5.6. Synthesis of MerremosideD
			2.14.5.7. Synthesis of Mezzettiaside
		2.14.6. Conclusion
		References
	2.15 Protecting Group Manipulations in Carbohydrate Synthesis
		2.15.1. Introduction
		2.15.2. Specific aspects of protecting group selection- epitheton ornans of protecting groups
		2.15.3. Methods for the regioselective protection of a hydroxylgroup
			2.15.3.1. Utilization of the different reactivity of the hydroxyl groups
			2.15.3.2. Introduction of the protecting groups by phase-transfer catalysis
			2.15.3.3. Regioselective protection through cyclic stannylene acetal or boronic ester intermediates and by transition met ...
			2.15.3.4. Regioselective protection by or through cyclic protecting groups
				2.15.3.4.1. Differentiation between 1,2- and 1,3-diols and between cis and trans vicinal diols by cyclic acetals
				2.15.3.4.2. Cyclic orthoester
				2.15.3.4.3. Carbonate and boronate protection
				2.15.3.4.4. Internal protecting groups
		2.15.4. Specific hydroxyl protecting groups
			2.15.4.1. Ether protecting groups
				2.15.4.1.1. The benzylether
				2.15.4.1.2. The p-methoxybenzyl, 2-naphthylmethyl, and other benzyl- and hetarylmethyl-type ethers
				2.15.4.1.3. The triphenylmethyl ethers
				2.15.4.1.4. The diphenylmethyl (DPM) and 9-fluorenyl ethers
				2.15.4.1.5. The allyl ethers
				2.15.4.1.6. Propargyl ethers
				2.15.4.1.7. The silyl ethers
					2.15.4.1.7.1. The TBDMS and TBDPS ethers
					2.15.4.1.7.2. The TIPS and other bulky silyl ethers
				2.15.4.1.8. The acetal protecting groups often discussed as ethers
			2.15.4.2. Esters
				2.15.4.2.1. The acetates
				2.15.4.2.2. The benzoates
				2.15.4.2.3. The pivaloates
				2.15.4.2.4. The levulinates
				2.15.4.2.5. The carbonates
			2.15.4.3. Cyclic acetals
				2.15.4.3.1. Isopropylidene acetals
				2.15.4.3.2. Aromatic acetals
				2.15.4.3.3. Diacetals
				2.15.4.3.4. Regioselective reductive opening of dioxane-type arylidene acetals
				2.15.4.3.5. Regioselective reductive opening of dioxolane-type arylidene acetals
				2.15.4.3.6. Oxidative cleavage of dioxane- and dioxolane-type benzylidene acetals
		2.15.5. Protection of amines
			2.15.5.1. Amides
			2.15.5.2. Imides
			2.15.5.3. Carbamates
			2.15.5.4. Azides
		2.15.6. One-pot methods
		2.15.7. The manifold role of protecting groups in oligosaccharide synthesis
			2.15.7.1. The effect of the protecting group on the reactivity and stereochemistry
			2.15.7.2. Protecting groups for monitoring the solid-phase oligosaccharide synthesis
				2.15.7.2.1. NMR approaches
				2.15.7.2.2. Colorimetric protecting groups
			2.15.7.3. Protecting groups as purificationtags
				2.15.7.3.1. Fluorinated protecting groups
				2.15.7.3.2. Catch-and-release purification
		2.15.8. Conclusions and outlook
		References
	2.16 Chemo-Enzymatic Syntheses of Oligosaccharides and Glycoconjugates
		2.16.1. Introduction
		2.16.2. Chemo-enzymatic syntheses of oligosaccharides
			2.16.2.1. General protocols of oligosaccharides syntheses
			2.16.2.2. Chemo-enzymatic syntheses of oligosaccharides of glycoproteins and glycopeptides
			2.16.2.3. Chemo-enzymatic synthesis of tumor associated carbohydrate antigens
			2.16.2.4. Synthesis of functional glycopolymer
		2.16.3. Chemo-enzymatic syntheses of glycoconjugates
			2.16.3.1. Fundamental process of chemo-enzymatic syntheses of glycoconjugates
			2.16.3.2. Improvement of endoglycosidase-catalyzed reactions by using engineered enzymes and modified donor substrates
			2.16.3.3. Chemo-enzymatic syntheses of glycopeptides
			2.16.3.4. Chemo-enzymatic synthesis of glycoproteins
			2.16.3.5. Chemo-enzymatic remodeling of glycoproteins
		2.16.4. Chemo-enzymatic glycoengineering of IgG antibody
		2.16.5. Chemo-enzymatic syntheses of O-glycan glycopeptides
		2.16.6. Perspective
		References
	2.17 Automated Oligosaccharide Synthesis: Development of the Glyconeer
		2.17.1. Introduction
		2.17.2. Designing a new automated oligosaccharide synthesis platform
			2.17.2.1. Why do we need a special automated platform for oligosaccharide synthesis?
			2.17.2.2. Why solid phase platforms?
			2.17.2.3. What are the specific challenges associated with solid phaseAGA?
			2.17.2.4. What is the potential of the development ofAGA?
			2.17.2.5. Other platforms used for the automated synthesis of oligosaccharides
				2.17.2.5.1. Programmed one-pot synthesis
				2.17.2.5.2. Automated fluoro-tag assisted solution phase synthesis
				2.17.2.5.3. HPLC-assisted automated oligosaccharide synthesis
		2.17.3. Previously constructed AGA platforms
			2.17.3.1. Peptide synthesizer platform modified forAGA
			2.17.3.2. Home built AGA synthesizer
		2.17.4. The design of the Glyconeer
			2.17.4.1. Main parts/technique
			2.17.4.2. Operating system
		2.17.5. Main modules
		2.17.6. First steps optimization
		2.17.7. Running the Glyconeer
			2.17.7.1. Preparation of the machine
			2.17.7.2. Programming and execution of a syntheticrun
		2.17.8. Examples for synthesis of oligosaccharides on the Glyconeer
			2.17.8.1. Synthesis of bacterial antigens
			2.17.8.2. Synthesis of complex glycans using Glyconeer
			2.17.8.3. Synthesis of oligorhamnan using disaccharideBBs
			2.17.8.4. Development of new photocleavage procedures
			2.17.8.5. Synthesis ofGAGs
		2.17.9. BBs and linkers used on the Glyconeer
		2.17.10. Concluding remarks
			2.17.10.1. Flexibility
			2.17.10.2. Limitations
			2.17.10.3. Outlook
		References
	2.18 Automated Oligosaccharide Synthesis: The Past, Present, and Future
		2.18.1. Introduction
		2.18.2. Part 1-History (until2001)
			2.18.2.1. The concept of solid-phase synthesis
			2.18.2.2. The automation concept
			2.18.2.3. Solid-phase peptide synthesis(SPSS)
			2.18.2.4. Automated peptide synthesis
			2.18.2.5. Solid-phase and automated DNA synthesis
		2.18.3. Automated oligosaccharide synthesis in the 21st century
			2.18.3.1. General considerations in carbohydrate synthesis
				2.18.3.1.1. Anomeric leaving groups and glycosylation activators
				2.18.3.1.2. Protecting groups as directing groups
				2.18.3.1.3. Programmable one-pot oligosaccharide synthesis
			2.18.3.2. Solid-phase oligosaccharide synthesis as the basis for automation
				2.18.3.2.1. Overall synthetic strategy
				2.18.3.2.2. The solidphase
				2.18.3.2.3. Linker
					2.18.3.2.3.1. Acid-base labile
					2.18.3.2.3.2. Metathesis labile
					2.18.3.2.3.3. Photocleavable linkers
				2.18.3.2.4. Building blocks
			2.18.3.3. Automated glycan assembly(AGA)
				2.18.3.3.1. Seminalwork
				2.18.3.3.2. Blood group antigens
				2.18.3.3.3. Glycosaminoglycans
				2.18.3.3.4. Very long polysaccharides
			2.18.3.4. Summary ofAGA
			2.18.3.5. Automated enzymatic synthesis
				2.18.3.5.1. Combined enzymatic synthesis andAGA
			2.18.3.6. Automated HPLC-assisted synthesis
			2.18.3.7. Automated solution-phase synthesis
				2.18.3.7.1. Fluorous tag-assisted
					2.18.3.7.1.1. β-Mannuronate and β-mannan
					2.18.3.7.1.2. Rhamnans and rhamnan sulfates di- and trisaccharides
				2.18.3.7.2. Electrochemical
			2.18.3.8. Summary
		2.18.4. The future of automated oligosaccharide synthesis
			2.18.4.1. Building block access
			2.18.4.2. Improved synthesis of complex polysaccharides
			2.18.4.3. Combing AGA with automated enzymatic synthesis
			2.18.4.4. Closing remarks
		References
	2.19 Ionic Liquid Tags for Supported Oligosaccharide Synthesis
		2.19.1. Introduction
		2.19.2. Ionic liquid supports
		2.19.3. Ester-linked ITags at the C-4 and C-6 position
		2.19.4. Ether-linked ITags at the anomeric position
		2.19.5. Ether-linked ITags at the C-6 position
		2.19.6. Amide-linkedITags
		2.19.7. ITag assisted chemo-enzymatic oligosaccharide synthesis
		2.19.8. Conclusions
		References
	2.20 HPLC-Based Automated Oligosaccharide Synthesis
		2.20.1. Introduction
		2.20.2. Generation A: Original automation set-up with ternarypump
		2.20.3. Generation B: Implementation of a quaternary pump and an autosampler
		2.20.4. Generation C: Implementation of the two-way switch valve as a mode for complete automation
		2.20.5. Development of dedicated solid supports
			2.20.5.1. STICS: Surface-tethered iterative carbohydrate synthesis
			2.20.5.2. PanzaGel resin for glycan synthesis
		2.20.6. Conclusions and outlook
		References
	2.21 Synthesis of Carbohydrate Building Blocks for Automated Oligosaccharide Construction
		2.21.1. Introduction
		2.21.2. Diversity of carbohydrate building blocks
		2.21.3. Carbohydrate nomenclature for humans and computers/automation platforms
		2.21.4. Automation of building block synthesis using continuous flow reactors
		2.21.5. Physical properties of carbohydrate building blocks and their protecting groups
			2.21.5.1. Solubility of carbohydrates and their derivatives
			2.21.5.2. Effect of the temperature of solvent on carbohydrate solubility
			2.21.5.3. Physical properties of sugar building blocks imparted by protecting groups
		2.21.6. Design of the synthesis of carbohydrate building blocks
		2.21.7. Blocking of competing reactive groups
			2.21.7.1. Protection of the primary hydroxyl
				2.21.7.1.1. Trityl ethers
				2.21.7.1.2. Silyl ethers
				2.21.7.1.3. Sulfonylation of primary hydroxyl groups
			2.21.7.2. Protection of the secondary hydroxyl
				2.21.7.2.1. Benzyl and substituted benzyl ethers
				2.21.7.2.2. Esters
			2.21.7.3. Protection of the anomeric hydroxyl
				2.21.7.3.1. Alkyl protecting groups
				2.21.7.3.2. Esters at the anomeric position
			2.21.7.4. Cyclic acetals, ketals, and orthoesters
		2.21.8. Controlling furanose versus pyranoseforms
			2.21.8.1. Synthesis of furanosides
			2.21.8.2. Solvent polarity to influence furanoside formation
		2.21.9. Strategies for selective protecting group removal
			2.21.9.1. Protecting group removal under acidic conditions
				2.21.9.1.1. Silyl ethers
				2.21.9.1.2. Trityl
			2.21.9.2. Protecting group removal under basic conditions
				2.21.9.2.1. Acetate esters
				2.21.9.2.2. Chloroacetate
				2.21.9.2.3. Levulinoyl esters
				2.21.9.2.4. Fluorenylmethoxy carbonyl(Fmoc)
			2.21.9.3. Protecting group removal under oxidative conditions
			2.21.9.4. Protecting group removal under reductive conditions
			2.21.9.5. Protecting group removal under radical conditions and usinglight
		2.21.10. Selection of anomeric groups/activation chemistry
		2.21.11. Groups for ease of detection and purification
			2.21.11.1. Protecting groups for purification
			2.21.11.2. Protecting groups for detection in HPLC protocols
		2.21.12. Protecting group strategies to string building blocks together in automation platforms
			2.21.12.1. Manual versus automated methods
			2.21.12.2. One-pot synthesis and prediction algorithms for carbohydrate building blocks
			2.21.12.3. Electrochemical
			2.21.12.4. Solid-phase-based automated glycan synthesis
			2.21.12.5. Fluorous-based solution-phase automated glycan synthesis
		2.21.13. Conclusions and future directions
		References
		Relevant Websites
	2.22 Bioorthogonal Chemical Ligations Towards Neoglycoproteins
		2.22.1. Introduction
		2.22.2. Structure and biological functions of glycans displayed on proteins
		2.22.3. Carbonyl-based bioorthogonal ligations for the preparation of neoglycoproteins
			2.22.3.1. Oxime and hydrazone ligations
			2.22.3.2. Reductive amination using lysine residues of peptides and proteins
		2.22.4. Palladium-catalyzed Suzuki-Miyaura cross-coupling for the preparation of neoglycoproteins
		2.22.5. Copper-catalyzed alkyne-azide cycloadditions (CuAAC) for the preparation of neoglycoproteins
			2.22.5.1. Azido-sugars and alkyno-polypeptides
			2.22.5.2. Alkyno-sugars and azido-polypeptides
		2.22.6. Strain-promoted alkyne-azide cycloadditions (SPAAC) for the preparation of neoglycoproteins
			2.22.6.1. Cyclooctyno-sugars and azido-polypeptides
			2.22.6.2. Azido-sugars and cyclooctyno-polypeptides
		2.22.7. Sequential bioorthogonal reactions for enhancing the speed and efficiency of the glycoconjugationstep
			2.22.7.1. Strain-promoted alkyne-azide cycloaddition coupled with lysine-specific RIKENclick
			2.22.7.2. Copper-catalyzed alkyne-azide cycloaddition coupled with inverse electron-demand Diels-Alder reaction
		2.22.8. Conclusion and future perspectives
		References
	2.23 Conjugation Techniques and Linker Strategies for Carbohydrate-Based Vaccines
		2.23.1. Introduction
			2.23.1.1. Carbohydrate-based vaccines
			2.23.1.2. Polysaccharide vaccines: Merits and limits
			2.23.1.3. Glycoconjugate vaccines: Background and mechanism of action
			2.23.1.4. Conjugation chemistry for carbohydrate-based vaccines
				2.23.1.4.1. Functional group accessible for conjugation
				2.23.1.4.2. Conjugation techniques
				2.23.1.4.3. Optimizing the design of a glycoconjugate vaccine
		2.23.2. Strategies for sugar modification
			2.23.2.1. Random activation
			2.23.2.2. Selective activation
		2.23.3. Linker strategies
			2.23.3.1. Zero-length crosslinkers
			2.23.3.2. Homobifunctional crosslinkers
			2.23.3.3. Heterobifunctional crosslinkers
		2.23.4. Strategies for protein conjugation
			2.23.4.1. Random protein conjugation
			2.23.4.2. Regioselective protein conjugation
				2.23.4.2.1. Site-selective chemical conjugation of natural aminoacids
				2.23.4.2.2. Site-selective enzymatic conjugation of natural aminoacids
				2.23.4.2.3. Site-selective conjugation of unnatural aminoacids
			2.23.4.3. Glycoproteins bioengineering
				2.23.4.3.1. Glycoprotein chemoenzymatic remodeling
		2.23.5. Conclusions
		References
	2.24 Enzyme-Based Methods to Synthesize Homogeneous Glycosaminoglycan Oligosaccharides
		2.24.1. Overview of glycosaminoglycans
		2.24.2. Biosynthesis and chemoenzymatic synthesis ofHS
			2.24.2.1. Chemoenzymatic synthesis ofHS
			2.24.2.2. Elongation
			2.24.2.3. C5-Epimerization and 2-O-sulfation
			2.24.2.4. 6-O-Sulfation
			2.24.2.5. 3-O-Sulfation
		2.24.3. Expression and purification of HS biosynthetic enzymes for the chemoenzymatic synthesis
			2.24.3.1. Co-factor synthesis
			2.24.3.2. Preparation of synthetic heparin using the chemoenzymaticmethod
		2.24.4. Enzymatic synthesis ofCS
		2.24.5. Conclusions
		Competing Interests
		References
	Back Cover
9780128222447_WEB03
	Front Cover
	Comprehensive Glycoscience
	Copyright
	Editor Biographies
		Editor-in-Chief
		Volume Editors
	List of Contributors for Volume 3
	Preface
	Contents of Volume 3
	Permission Acknowledgement
	3.01 Folding and Quality Control of Glycoproteins
		3.01.1. Introduction
			3.01.1.1. ERQC, ERAD and ER-phagy
			3.01.1.2. N-glycosylation: Not simply an accessory
		3.01.2. N-glycan dependent quality control-Early events
			3.01.2.1. Oligosaccharyltransferase(OST)
			3.01.2.2. α-Glucosidases I/II and Malectin
			3.01.2.3. Calnexin (CNX)/Calreticulin (CRT)Cycle
			3.01.2.4. Interaction of CNX/CRT with folding-assisting proteins
			3.01.2.5. UDP-Glucose:Glycoprotein glucosyltransferase (UGGT): Afoldingsensor
			3.01.2.6. Is CNX/CRT cycle required for the general folding of glycoproteins?
		3.01.3. Effect of man trimming on the degradation and transport of glycoproteins
			3.01.3.1. Mns1/MAN1B1
			3.01.3.2. EDEM, a membrane protein that enhances glycoproteinERAD
			3.01.3.3. OS-9, a bona fide ``Degradation Lectin´´
			3.01.3.4. Lectin cargo receptors: Glyco-specific transport
			3.01.3.5. Is vesicular transport required for efficient glycoproteinERAD?
		3.01.4. Retrotranslocation and cytosolic events of glycoproteinERAD
			3.01.4.1. Substrate recognition and retrotranslocation
			3.01.4.2. Sugar-recognizing ubiquitin ligases (FBS proteins)
			3.01.4.3. Cytosolic peptide:N-glycanases(NGLY1)
		3.01.5. Perspectives
		Acknowledgment
		References
	3.02 Biosynthesis and Degradation of Glycans of the Extracellular Matrix: Sulfated Glycosaminoglycans, Hyaluronan, and Matriglycan
		3.02.1. Introduction
		3.02.2. Biosynthesis of CS and HS GAG chains
		3.02.3. Biosynthesis of the GAG-protein linkage region tetrasaccharides for CS and HS GAG chains
			3.02.3.1. Biosynthesis of the GAG-protein linkage region tetrasaccharides
			3.02.3.2. Impairment of glycosyltransferases involved in the biosynthesis of GAG-protein linkage region tetrasaccharides  ...
		3.02.4. Biosynthesis of the GAG backbones of the CS and HS chains
			3.02.4.1. Biosynthesis of the Chn backbone
			3.02.4.2. Biosynthesis of the HS backbone
			3.02.4.3. Impairment of enzymes involved in backbone synthesis of Chn and HS chains
				3.02.4.3.1. The essential role of Chn/CS in embryonic cell division
				3.02.4.3.2. Mice deficient in enzymes involved in Chn backbone synthesis
				3.02.4.3.3. Human genetic disorders caused by mutation in ChSy-1 and ChGn-1
				3.02.4.3.4. Mice deficient in enzymes involved in HS backbone synthesis
				3.02.4.3.5. Human genetic disorders caused by enzymes involved in HS backbone synthesis
		3.02.5. Modifications of CS and HS GAG chains
			3.02.5.1. Enzymes involved in sulfation and epimerization of CS chains
			3.02.5.2. Enzymes involved in HS-specific modifications
			3.02.5.3. Impairment of enzymes involved in CS-specific modifications in mice and humans
			3.02.5.4. Impairment of enzymes involved in HS-specific modifications in mice and humans
		3.02.6. Fine-tuning of biosynthesis of CS and HS GAG chains
			3.02.6.1. Transient Xyl phosphorylation of the tetrasaccharide linkage region
			3.02.6.2. Alternative biosynthetic machineries for regulating the amount of CS chains
			3.02.6.3. 3-O-Sulfation of the non-reducing terminal GlcA in the linkage region
		3.02.7. Biosynthesis and functions of KS chains
		3.02.8. Biosynthesis and functions of HA chains
		3.02.9. GAG catabolism
			3.02.9.1. Lysosomal enzymes involved in exolytic degradation of GAG chains
			3.02.9.2. CS catabolism
				3.02.9.2.1. Endoglycosidase(s)in CS catabolism
				3.02.9.2.2. Sequential degradation of CS oligosaccharides by exo-acting lysosomal enzymes
			3.02.9.3. HS catabolism
			3.02.9.4. KS catabolism
			3.02.9.5. HA catabolism
				3.02.9.5.1. Canonical machineries for HA catabolism
				3.02.9.5.2. Non-canonical machineries for HA catabolism
		3.02.10. Matriglycan biosynthesis
		3.02.11. Modes of action of GAG chains
			3.02.11.1. Conventional mechanisms of action of CS chains as a passive extracellular scaffold
				3.02.11.1.1. CS chains as cell surface receptors for pathogens
				3.02.11.1.2. CS chains as co-receptors and/or signal modulators
				3.02.11.1.3. CS sulfation pattern-dependent neuronal plasticity
				3.02.11.1.4. CS abundance in myogenic differentiation/regeneration
			3.02.11.2. CS chains as extracellular signaling molecules
				3.02.11.2.1. CS chains in neuronal extension and regeneration
				3.02.11.2.2. CS chains in osteogenesis
				3.02.11.2.3. CS chains in stem cell biology
				3.02.11.2.4. CS chains in metastasis
		3.02.12. Perspectives
		Acknowledgment
		References
	3.03 Biology of Proteoglycans and Associated Glycosaminoglycans
		3.03.1. Introduction
		3.03.2. Biosynthesis of protein attachedGAGs
			3.03.2.1. Heparan sulfate and heparin biosynthesis
			3.03.2.2. Chondroitin and dermatan sulfate biosynthesis
			3.03.2.3. Keratan sulfate
			3.03.2.4. Disorders associated to GAG biosynthesis
		3.03.3. Proteoglycans
			3.03.3.1. Intracellular
				3.03.3.1.1. Serglycin
			3.03.3.2. Cell surface proteoglycans
				3.03.3.2.1. Glypicans
				3.03.3.2.2. Glypican-1
				3.03.3.2.3. Glypican-2
				3.03.3.2.4. Glypican-3
				3.03.3.2.5. Glypican-4
				3.03.3.2.6. Glypican-5
				3.03.3.2.7. Glypican-6
				3.03.3.2.8. Syndecans
				3.03.3.2.9. Syndecan1
				3.03.3.2.10. Syndecan2
				3.03.3.2.11. Syndecan3
				3.03.3.2.12. Syndecan-4
				3.03.3.2.13. NG2
				3.03.3.2.14. Betaglycan
				3.03.3.2.15. Phosphacan
				3.03.3.2.16. SV2
				3.03.3.2.17. Claustrin
				3.03.3.2.18. PG1000
				3.03.3.2.19. Abakan
				3.03.3.2.20. CD44
				3.03.3.2.21. CD74
			3.03.3.3. Pericellular
				3.03.3.3.1. Perlecan
				3.03.3.3.2. Agrin
				3.03.3.3.3. Collagen IX type a2chain
				3.03.3.3.4. CollagenXV
				3.03.3.3.5. CollagenXVIII
			3.03.3.4. Extracellular
				3.03.3.4.1. The lectican family (Hyalectans)
				3.03.3.4.2. Aggrecan
				3.03.3.4.3. Versican
				3.03.3.4.4. Neurocan
				3.03.3.4.5. Brevican
				3.03.3.4.6. Small leucine rich proteoglycans(SLRP)
				3.03.3.4.7. Decorin
				3.03.3.4.8. Biglycan
				3.03.3.4.9. Fibromodulin
				3.03.3.4.10. Lumican
				3.03.3.4.11. Keratocan
				3.03.3.4.12. Osteoadherin
				3.03.3.4.13. Osteoglycin
				3.03.3.4.14. Testican/Spock
				3.03.3.4.15. Testican-1
				3.03.3.4.16. Testican-2
				3.03.3.4.17. Testican-3
				3.03.3.4.18. Endocan
		3.03.4. Summary
		References
	3.04 Glycosylphosphatidylinositol Anchors and Lipids
		3.04.1. Biosynthesis of GPI-anchored proteins in mammaliancells
			3.04.1.1. Introduction
			3.04.1.2. Structure of mammalianGPIs
			3.04.1.3. Overview of the GPI biosynthetic pathway
		3.04.2. Biosynthesis of GPI precursors
			3.04.2.1. Step 1: PI + UDP-GlcNAc  GlcNAc-PI +UDP
			3.04.2.2. Step 2: GlcNAc-PI + H2O  GlcN-PI + acetate
			3.04.2.3. Step 3: Flipping of GlcN-PI into the ERlumen
			3.04.2.4. Step 4: GlcN-PI + acyl-CoA  GlcN-(acyl)PI +CoA
			3.04.2.5. Step 5: Diacyl to alkyl-acyl lipid exchange
			3.04.2.6. Step 6: GlcN-(acyl)PI + Dol-P-Man  Manα1,4-GlcN-(acyl)PI + Dol-P
			3.04.2.7. Step 7: Dol-P + GDP-Man  Dol-P-Man +GDP
			3.04.2.8. Step 8: Man-α1,4-GlcN-(acyl)PI + Dol-P-Man  Man-α1,6-Man-α1,4-GlcN-(acyl)PI + Dol-P
			3.04.2.9. Step 9: Man-α1,6-Man-α1,4-GlcN-(acyl)PI + PE  Man-α1,6-(EtN-P-2)Man-α1,4-GlcN-(acyl)PI + diacylglycerol
			3.04.2.10. Step 10: Man-α1,6-(EtN-P-2)Man-α1,4-GlcN-(acyl)PI + Dol-P-Man  Man-α1,2-Man-α1,6-(EtN-P-2)Man-α1,4-GlcN-(acyl) ...
			3.04.2.11. Step 11: Man-α1,2-Man-α1,6-(EtN-P-2)Man-α1,4-GlcN-(acyl)PI + Dol-P-Man  Man-α1,2-Man-α1,2-Man-α1,6-(EtN-P-2)Ma ...
			3.04.2.12. Step 12: Man-α1,2-Man-α1,6-(EtN-P-2)Man-α1,4-GlcN-(acyl)PI + PE  EtN-P-6-Man-α1,2-Man-α1,6-(EtN-P-2)Man-α1,4-G ...
			3.04.2.13. Step 13: EtN-P-6-Man-α1,2-Man-α1,6-(EtN-P-2)Man-α1,4-GlcN-(acyl)PI + PE  EtN-P-6-Man-α1,2-(EtN-P-6)Man-α1,6-(E ...
			3.04.2.14. Step 14: Attachment of GPI to proteins: GPI complete precursor + pro-protein  GPI-AP + signal peptide
		3.04.3. GPI-anchor remodeling, GPI-AP transport, shedding, and quality control
			3.04.3.1. Step15: Inositol deacylation from nascent GPI-APs
			3.04.3.2. Step 16: Removal of EtN-P from Man2 of GPI-anchors
			3.04.3.3. Step 17: Export of GPI-APs from the ER to the Golgi apparatus
			3.04.3.4. Step 18and 19: Fatty acid remodeling in the Golgi apparatus
			3.04.3.5. Step 20: Addition of a GalNAc side-chain toMan1
			3.04.3.6. Step 21: Addition of Gal to the GalNAc side-chain
			3.04.3.7. Lipid raft association of GPI-APs
			3.04.3.8. Release of GPI-APs from plasma membrane
			3.04.3.9. Quality control and degradation of misfolded GPI-APs
		3.04.4. FreeGPI
		3.04.5. Conclusion
		Acknowledgment
		References
	3.05 Biosynthesis of Glycolipids
		3.05.1. Introduction
		3.05.2. GalCer and its extensions: Sulfatide, GM4 and galabiosylceramide
		3.05.3. GlcCer, lactosylceramide (LacCer) and LacCer-based GSL families
		3.05.4. Globo-series extensions
		3.05.5. Lacto/neolacto-series extensions
		3.05.6. Ganglio-series extensions
		3.05.7. Glycoglycerolipids
		3.05.8. Perspective
		References
	3.06 Nucleocytoplasmic Protein Glycosylation
		3.06.1. Introduction
		3.06.2. O-GlcNAc cycling enzymes
			3.06.2.1. Biochemistry of O-GlcNAc transferase(OGT)
				3.06.2.1.1. OGT catalytic mechanisms
				3.06.2.1.2. Other activities ofOGT
				3.06.2.1.3. OGT structures and substrate recognition
			3.06.2.2. Biochemistry of O-GlcNAcase(OGA)
				3.06.2.2.1. OGA catalytic mechanism
				3.06.2.2.2. OGA structures and substrate recognition
			3.06.2.3. Regulation of OGT andOGA
				3.06.2.3.1. Transcriptional/post-transcriptional regulation
				3.06.2.3.2. Post-translational regulation
				3.06.2.3.3. Regulation by protein-protein interactions and translocalization
		3.06.3. O-GlcNAc biology
			3.06.3.1. Signal transduction
				3.06.3.1.1. Cross-talk with kinase and phosphatase signaling
				3.06.3.1.2. Interaction with protein ubiquitination and degradation
				3.06.3.1.3. Other signaling mechanisms
			3.06.3.2. Gene expression
				3.06.3.2.1. Transcriptional regulation
				3.06.3.2.2. Post-transcriptional regulation
				3.06.3.2.3. Translational regulation
			3.06.3.3. Cell cycle and cytoskeletal regulation
				3.06.3.3.1. Cellcycle
				3.06.3.3.2. Cytoskeleton
			3.06.3.4. Mitochondria
			3.06.3.5. Apoptosis
			3.06.3.6. O-GlcNAc dysregulation
		3.06.4. Other examples of nucleocytoplasmic glycosylation
			3.06.4.1. O-mannosylation inyeast
			3.06.4.2. Glycogen/Glycogenin
			3.06.4.3. Skp1/hydroxyproline
		3.06.5. Nucleocytoplasmic glycosylation by pathogenic bacterial toxins
			3.06.5.1. Toxins targeting Rho family GTPases
			3.06.5.2. Legionella pneumophila toxins
			3.06.5.3. Enteropathogenic E.coliNleB
			3.06.5.4. Prospects for bacterial toxin glycosylation
		Acknowledgment
		References
	3.07 Biosynthesis of Bacterial Polysaccharides
		3.07.1. Introduction
		3.07.2. Glycosyltransferases
			3.07.2.1. Glycosyltransferase assays
			3.07.2.2. Synthesis of nucleotide sugar donor substrates
			3.07.2.3. Synthesis of acceptor substrates
			3.07.2.4. Glycosyltransferase mechanisms
		3.07.3. Protein glycosylation in bacteria
			3.07.3.1. Protein N-glycosylation
			3.07.3.2. Protein O-glycosylation
				3.07.3.2.1. O-glycosylation using a lipid carrier
				3.07.3.2.2. Tyr O-glycosylation in Paenibacillus alvei
				3.07.3.2.3. O-glycosylation in Geobacillus stearothermophilus
				3.07.3.2.4. Stepwise O-glycosylation pathways
		3.07.4. Peptidoglycan synthesis
		3.07.5. Teichoic and lipoteichoicacids
		3.07.6. Assembly of secondary cell wall polysaccharides
		3.07.7. Capsular polysaccharides in Gram positive bacteria
		3.07.8. Polysaccharide synthesis in Gram negative bacteria
			3.07.8.1. Polysialic acid capsules
			3.07.8.2. The enterobacterial common antigen
			3.07.8.3. Biosynthesis of beta-glucans
		3.07.9. Lipopolysaccharides of Gram negative bacteria
		3.07.10. Biosynthesis of LPS core oligosaccharides
		3.07.11. O antigen assembly by the Wzy polymerase pathway
		3.07.12. O antigen assembly by the ABC transporter pathway
		3.07.13. Synthase pathway of Oantigen synthesis
		3.07.14. Glycosyltransferases involved in Oantigen synthesis
			3.07.14.1. Enzymatic synthesis of the Oantigen repeating unit of E.coli serotype O104:H4
			3.07.14.2. Blood group-containing Oantigen synthesis in bacteria
			3.07.14.3. Klebsiella pneumoniae Oantigen
			3.07.14.4. Pseudomonas aeruginosa Oantigen
		3.07.15. Glycosylation pathways used in vaccine development
		3.07.16. Conclusions
		Acknowledgment
		References
	3.08 The Structure and Biosynthesis of Glycans in the Parasitic Protists
		3.08.1. Introduction
		3.08.2. Trypanosomatid parasites
			3.08.2.1. Overview of the surface coats of trypanosomatid parasites
			3.08.2.2. GPI glycolipids
				3.08.2.2.1. GPI protein anchors
				3.08.2.2.2. Free GPIs andGIPLs
				3.08.2.2.3. Leishmania lipophosphoglycan (LPG) and Crithidia lipoarabinogalactan (LAG)
			3.08.2.3. N-glycans
				3.08.2.3.1. Dolichol-linked oligosaccharides
				3.08.2.3.2. Processing of N-glycans in the ER andERAD
				3.08.2.3.3. Processing of N-glycans in theGolgi
			3.08.2.4. O-glycans
				3.08.2.4.1. T.cruzi mucins
				3.08.2.4.2. O-glucosylation ofVSG
			3.08.2.5. O-phosphoglycosylation
				3.08.2.5.1. Leishmania proteophosphoglycans
				3.08.2.5.2. T.cruzi gp72 and NETNES
			3.08.2.6. Glucosylation ofDNA
			3.08.2.7. Reserve polysaccharides
				3.08.2.7.1. Mannogen biosynthesis
			3.08.2.8. Sugar nucleotide and lipid-linked donor biosynthesis
		3.08.3. Apicomplexan parasites
			3.08.3.1. Overview of apicomplexan parasite surfacecoats
			3.08.3.2. GPI glycolipids
				3.08.3.2.1. Protein-linkedGPI
				3.08.3.2.2. Free GPI glycolipid
			3.08.3.3. N-glycans
				3.08.3.3.1. Dolichol-linked oligosaccharides andERAD
			3.08.3.4. O-glycans (secretory proteins)
				3.08.3.4.1. Toxoplasma O-GalNAc mucin-like glycans
				3.08.3.4.2. O-fucosylation and C-mannosylation ofTRP
			3.08.3.5. O-glycosylation of cytoplasmic proteins
				3.08.3.5.1. O-fucosylation of nucleocytoplasmic proteins
			3.08.3.6. Hydroxyproline-linked glycans
			3.08.3.7. Reserve and cell wall polysaccharides
				3.08.3.7.1. Amylopectin and trehalose
				3.08.3.7.2. Cyst wall glucans
			3.08.3.8. Sugar nucleotide biosynthesis
		3.08.4. Archamoeba and Metamonada
			3.08.4.1. GPIs
			3.08.4.2. N-glycans
			3.08.4.3. O-glycans
			3.08.4.4. O-Phosphoglycosylation
			3.08.4.5. Reserve and cyst wall polysaccharides
		3.08.5. Conclusions
		Acknowledgment
		References
	3.09 Controlling Glycosyltransferase Activity: Inhibition and Enzyme Engineering
		3.09.1. Introduction
			3.09.1.1. Leloir versus non-Leloir GTs and their donor substrates
			3.09.1.2. Sequence-based CAZy families and structural categorization ofGTs
			3.09.1.3. Mechanism ofGTs
				3.09.1.3.1. Inverting GT mechanisms
				3.09.1.3.2. Retaining GT mechanisms
		3.09.2. Inhibition of GT activity
			3.09.2.1. Types of GT inhibitors
				3.09.2.1.1. GT substrate analogs and transition state analogs
				3.09.2.1.2. Glycomimetic inhibitors ofGTs
				3.09.2.1.3. Natural products as GT inhibitors
				3.09.2.1.4. Structurally diverse synthetic small molecules as GT inhibitors
			3.09.2.2. High-throughput screening strategies to identify GT inhibitors
				3.09.2.2.1. Coupled enzyme assays that measure GT activity by nucleotide release
				3.09.2.2.2. Carbohydrate microarray-based GT assays
				3.09.2.2.3. Fluorescence polarization-based GT assays
				3.09.2.2.4. A direct fluorescent assay for GT activity using fluorophore-tagged sugar donors
				3.09.2.2.5. A glycosidase-dependent fluorescent coupled GTassay
		3.09.3. GT activity engineering
			3.09.3.1. Modifying GT activity using rational protein design
				3.09.3.1.1. Targeted mutagenesis ofGTs
				3.09.3.1.2. Domain swapping to generate GT chimeras
			3.09.3.2. High-throughput screening strategies and their application to discover and engineer GT activity
				3.09.3.2.1. A plate-based fluorescence quenching strategy for the directed evolution of natural productGTs
				3.09.3.2.2. Intracellular fluorescence entrapment to screen GT activity byFACS
				3.09.3.2.3. Glycan-binding proteins to screen GT activity in plate- and particle-based invitro assays and FACS-based invi ...
		3.09.4. Conclusions
		References
	3.10 Mucin-Type O-Glycans: Biosynthesis and Functions
		3.10.1. Introduction
		3.10.2. O-glycan core structures, extensions and epitopes
			3.10.2.1. Isolation and structural analyses of O-glycans
			3.10.2.2. Site specificity of mucin-type O-glycosylation
		3.10.3. Biosynthesis of O-glycans: Glycosyltransferases and sulfotransferases
			3.10.3.1. Folds and mechanisms of glycosyltransferases
			3.10.3.2. Polypeptide GalNAc-transferases
			3.10.3.3. Core 1 β3 Gal-transferase
			3.10.3.4. Core 2-4 GlcNAc-transferases
				3.10.3.4.1. Core 2 and 4 synthesis
				3.10.3.4.2. Core 3 synthesis
			3.10.3.5. Extension Gal-, GlcNAc- and GalNAc-transferases
				3.10.3.5.1. Extension GlcNAc-transferases
				3.10.3.5.2. β4-Gal-transferases
				3.10.3.5.3. β3-Gal-transferases
				3.10.3.5.4. β3- and β4-GalNAc-transferases
				3.10.3.5.5. Branching β6-GlcNAc-transferases
			3.10.3.6. Sulfotransferases
			3.10.3.7. Fucosyltransferases
				3.10.3.7.1. α2-Fuc-transferases
				3.10.3.7.2. α3- and α4-Fuc-transferases
			3.10.3.8. Sialyltransferases
				3.10.3.8.1. α3-Sialyltransferases
				3.10.3.8.2. α6-Sialyltransferases
				3.10.3.8.3. α8-Sialyltransferases
			3.10.3.9. Synthesis of blood groups and α-linked sugar epitopes
			3.10.3.10. Inhibitors
			3.10.3.11. Golgi localization and intracellular distributions of glycosyltransferases
			3.10.3.12. Comparison of human to bacterial glycosyltransferases
		3.10.4. Functions of mucin type O-glycans: Homeostasis and pathology
		3.10.5. Conclusions
		Acknowledgment
		References
	3.11 Imaging Glycans With Metabolic Glycoengineering
		3.11.1. Introduction
		3.11.2. Historical development of metabolic glycoengineering as a technique to labelcells
			3.11.2.1. Foundations of MGE derive from nonliving systems
			3.11.2.2. Increasing bioavailability
				3.11.2.2.1. Simplifying the chemical structure of MGE monosaccharide substrates
				3.11.2.2.2. Improving cell uptake by modifying the hydroxylgroup
			3.11.2.3. Bertozzi: Demonstration of bioorthogonal sugars
				3.11.2.3.1. Ketone-modified sialosides pioneer MGE bioorthogonal ligation reactions
				3.11.2.3.2. General considerations for bioorthogonal chemistry in living systems
		3.11.3. Bioorthogonal ligation strategies
			3.11.3.1. Azido-ligation reactions
			3.11.3.2. Expanding bioorthogonal ligation reactions beyond azido-sugars
				3.11.3.2.1. ``Reverse´´ click reactions
				3.11.3.2.2. Context-dependent biorthogonal reactions
				3.11.3.2.3. Photoactivated reactions
		3.11.4. MGE-based glycan imaging in living systems
			3.11.4.1. Invitro
			3.11.4.2. Invivo
				3.11.4.2.1. Whole body imaging
				3.11.4.2.2. Case study: Zebrafish development
				3.11.4.2.3. Case study: Brain sialosides
		3.11.5. Disease
			3.11.5.1. Cancer: The groundbreaking disease indication forMGE
			3.11.5.2. Imaging tumors
			3.11.5.3. Increasing specificity/selectivity
				3.11.5.3.1. The need for increased tumor selectivity
				3.11.5.3.2. Exploiting the EPR effect and tumor antigens through nanoencapsulation
				3.11.5.3.3. Exploiting tumor-specific enzymes
		3.11.6. Future directions
			3.11.6.1. Therapeutic and theranostics
				3.11.6.1.1. Therapeutics
				3.11.6.1.2. Toward theranostics
			3.11.6.2. Reaction rate versus bioorthogonal selectivity
				3.11.6.2.1. Toward high reaction rates compatible with living systems
				3.11.6.2.2. Additional MGE-compatible chemical reporters
				3.11.6.2.3. Tetrazine bioorthogonal ligation reactions
			3.11.6.3. Multiplexed MGE labeling
			3.11.6.4. MGE labeling in nonmammalian systems
				3.11.6.4.1. Insects
				3.11.6.4.2. Bacteria
				3.11.6.4.3. Plants
		3.11.7. Conclusions
		Acknowledgment
		Acknowledgment
		Acknowledgment
		Acknowledgment
		References
	3.12 Metabolic Engineering of Glycans
		3.12.1. Introduction
		3.12.2. Core N-linked glycosylation
			3.12.2.1. Core N-linked reporters
		3.12.3. Sialicacid
			3.12.3.1. Sialic acid reporters(MCRs)
			3.12.3.2. Sialic acid inhibitors(MCIs)
		3.12.4. Mucin O-linked glycosylation
			3.12.4.1. Mucin O-linked reporters(MCRs)
			3.12.4.2. Mucin O-linked inhibitors(MCIs)
		3.12.5. Fucose
			3.12.5.1. Fucose reporters(MCRs)
			3.12.5.2. Fucose inhibitors(MCIs)
		3.12.6. O-GlcNAc modification
			3.12.6.1. O-GlcNAc reporters(MCRs)
			3.12.6.2. O-GlcNAc inhibitors(MCIs)
		3.12.7. Glycosaminoglycan
			3.12.7.1. Glycosaminoglycan reporter/inhibitors (combination MCR/MCIs)
			3.12.7.2. Glycosaminoglycan inhibitors(MCIs)
		3.12.8. Conclusions and outlook
		References
	3.13 Transformative Technologies to Advance Our Understanding of the Functions of O-GlcNAc
		3.13.1. Introduction
		3.13.2. Bovine β-1,4-galactosyltransferase-The beginning
		3.13.3. Assays-Discovery of OGT andOGA
		3.13.4. Antibodies-Broad adoption
		3.13.5. Genetic models-The essential role of O-GlcNAc
		3.13.6. Chemical probes-A diverse toolkit
		3.13.7. Site-mapping
		3.13.8. Site-specific studies-A view to the future
		3.13.9. Concluding remarks
		References
	3.14 Metabolic Labeling of Bacterial Glycans
		3.14.1. Introduction
			3.14.1.1. The bioorthogonal chemical reporter strategy
			3.14.1.2. The major bioorthogonal reactions
		3.14.2. Glycans in the bacterial cell envelope
		3.14.3. Carbohydrate-derived chemical reporters for the study of the bacterial cell envelope
			3.14.3.1. Chemical reporters for the carbohydrate backbone in peptidoglycan
			3.14.3.2. Chemical reporters for glycoproteins
			3.14.3.3. Chemical reporters for lipopolysaccharides
			3.14.3.4. Chemical reporters for the mycomembrane
				3.14.3.4.1. Trehalose-based probes synthesis
				3.14.3.4.2. Trehalose-based probes applications
		3.14.4. Conclusion and outlook
		Acknowledgment
		References
	3.15 Nuclear Magnetic Resonance Techniques for the Study of Glycan Interactions
		3.15.1. Introduction
		3.15.2. NMR and molecular recognition
		3.15.3. trNOESY
		3.15.4. STD
		3.15.5. WaterLOGSY
		3.15.6. 19F based NMR experiments
		3.15.7. Other developments: ParamagneticNMR
		3.15.8. Conclusions
		Acknowledgment
		References
	3.16 Molecular and Mechanistic Basis of Lectin-Glycan Interactions
		3.16.1. Introduction
		3.16.2. Mechanism and examples of monovalent glycan-lectin interactions
			3.16.2.1. Factors that contribute to glycan binding by lectins
				3.16.2.1.1. Hydrogenbonds
					3.16.2.1.1.1. Contribution of hydrogen bonding to the thermodynamics of binding
						3.16.2.1.1.1.1. Involvement of additional hydrogen bonding in extended site interaction
						3.16.2.1.1.1.2. Non-additivity of the H and G values for deoxygenation at the hydroxyl groups of 1
						3.16.2.1.1.1.3. Homologous lectins with conserved binding sites interact with the same ligand through the same set of hyd ...
				3.16.2.1.2. Hydrophobic interactions
				3.16.2.1.3. Divalent metalions
				3.16.2.1.4. Water molecules
					3.16.2.1.4.1. Role of the ordered water molecule in the binding site ofConA
					3.16.2.1.4.2. Relative contribution of solvent to the enthalpy of binding of saccharides to ConA andDGL
					3.16.2.1.4.3. ITC measurements of carbohydrate binding to ConA under osmotic stress
					3.16.2.1.4.4. Role of water molecules in the extended binding sites of ConA andDGL
						3.16.2.1.4.4.1. Correlation of the H (H2O-D2O) data for analogs 2-11 with differences in the location of ordered water in ...
						3.16.2.1.4.4.2. Correlation of H (H2O-D2O) values of deoxy analogs of 1 with the number and strength of solvent hydrogen  ...
						3.16.2.1.4.4.3. Correlation of the H (H2O-D2O) data for Me αMan and Me αGlc with differences in the location of ordered w ...
						3.16.2.1.4.4.4. Lack of correlation of altered water structures in the DGL and ConA complexes with the core trimannoside  ...
				3.16.2.1.5. Ionic interactions
				3.16.2.1.6. Carbohydrate conformation
			3.16.2.2. Glycan binding mechanisms of different lectins
				3.16.2.2.1. Influenza virus hemagglutinin
				3.16.2.2.2. Legume lectins
				3.16.2.2.3. Cereal lectin
				3.16.2.2.4. Bulb lectins
				3.16.2.2.5. Galectins
				3.16.2.2.6. C-Type lectins
					3.16.2.2.6.1. Mannose binding proteins(MBPs)
					3.16.2.2.6.2. Selectins
				3.16.2.2.7. P-Type lectins
				3.16.2.2.8. Fucose binding lectins
					3.16.2.2.8.1. Anguilla anguilla agglutinin
					3.16.2.2.8.2. Bacterial and fungal lectins
				3.16.2.2.9. I-Type lectins
		3.16.3. Mechanistic basis of multivalent glycan-lectin interactions
			3.16.3.1. Intramolecular binding
				3.16.3.1.1. Asialoglycoprotein receptor
				3.16.3.1.2. Shiga-like toxin and choleratoxin
			3.16.3.2. Intermolecular binding
				3.16.3.2.1. Legume lectins and galectins
					3.16.3.2.1.1. Multivalent binding by legume lectins
						3.16.3.2.1.1.1. ITC determined n values are inversely proportional to the functional valency of multivalent carbohydrates
						3.16.3.2.1.1.2. H increases in direct proportion to the valency of multivalent carbohydrates binding to ConA andDGL
						3.16.3.2.1.1.3. TS does not directly increase in proportion to the valency of multivalent carbohydrates binding to ConA a ...
						3.16.3.2.1.1.4. Thermodynamic basis for enhanced affinities of multivalent analogs for ConA andDGL
						3.16.3.2.1.1.5. The epitopes of a multivalent carbohydrate possess a gradient of decreasing microscopic affinity constants
						3.16.3.2.1.1.6. Range of microscopic affinity constants for multivalent carbohydrates binding to ConA andDGL
					3.16.3.2.1.2. Binding of asialofetuin to galectins
						3.16.3.2.1.2.1. Range of microscopic Ka values for ASF binding to galectins
			3.16.3.3. Other examples of multivalent binding
				3.16.3.3.1. Interaction of lectins with multivalent polymeric ligands
				3.16.3.3.2. Multivalent inhibitors of influenza virus hemagglutinin(HA)
				3.16.3.3.3. Xenopus laevis lectinXL35
				3.16.3.3.4. Interaction of Cyanovirin-N with high mannose oligosaccharides
				3.16.3.3.5. Photoswitchable cluster glycosides
				3.16.3.3.6. Multivalent binding by garlic lectin
			3.16.3.4. Glycan-lectin cross-linking interactions
				3.16.3.4.1. Type-1 and Type-2 cross-linked complexes
				3.16.3.4.2. A multivalent carbohydrate can form a unique cross-linked complex with a lectin in the presence of other carb ...
				3.16.3.4.3. The structures of the carbohydrates and lectins determine their cross-linking properties
		3.16.4. Scaffolds of glycoconjugates are as important as their glycan epitopes
			3.16.4.1. Lectin binding entropy becomes more favorable when a free glycan is covalently attached to protein scaffolds
			3.16.4.2. Entropic advantage of glycosylation
			3.16.4.3. Scaffolds of glycoconjugates play a regulatory role in the kinetics of lattice formation
			3.16.4.4. Scaffolds can diversify the functions of glycoconjugates and their binding partners (lectins)
			3.16.4.5. Beyond affinity and valence effects
		3.16.5. Interaction of lectins with mucins
			3.16.5.1. Affinity of lectin-mucin interaction is proportional to the length of mucins
			3.16.5.2. Mechanisms of binding of lectins to mucins: The `bind-and-jumpmodel
		3.16.6. A lectin that behaves like Aglycosaminoglycan-binding protein
			3.16.6.1. Gal-3 binds to sulfated glycosaminoglycans and chondroitin sulfate proteoglycans
			3.16.6.2. The carbohydrate recognition domain of Gal-3 contains the GAG bindingsite
			3.16.6.3. GAGs bind to the lactose/LacNAc binding site of Gal-3
			3.16.6.4. CSA and CSC, not heparin and CSB, are multivalent ligands of Gal-3
			3.16.6.5. CSPG reversibly cross-links Gal-3 through multivalent binding
			3.16.6.6. Affinity of Gal-3 depends on the chain length ofGAGs
		3.16.7. Conclusions
		Acknowledgment
		References
	3.17 Design and Development of Divalent Lectin Ligands
		3.17.1. The case ofLecA
		3.17.2. Rigid or flexible spacers
		References
	3.18 Lectins as AnalyticalTools
		3.18.1. Introduction to lectins
		3.18.2. Families of lectins
			3.18.2.1. Plant lectins
				3.18.2.1.1. Biological functions
				3.18.2.1.2. Applications of plant lectins
			3.18.2.2. Microbial lectins
			3.18.2.3. Lectins in other organisms
				3.18.2.3.1. Animal lectins
				3.18.2.3.2. Virus lectins
				3.18.2.3.3. Parasite lectins
		3.18.3. Principles of carbohydrate recognition
			3.18.3.1. Structure-function relationships
			3.18.3.2. C-type lectins
			3.18.3.3. Legume lectins
		3.18.4. Lectin microarrays
			3.18.4.1. Principles
			3.18.4.2. Advances in technology
		3.18.5. Applications
			3.18.5.1. Analysis of glycosylation profiles of proteins, antibodies andcells
			3.18.5.2. Biomarker discovery and analysis
			3.18.5.3. Comparison of glycosylation pattern differences or alterations
			3.18.5.4. Therapeutic applications
		3.18.6. Outlook
		Acknowledgment
		References
	3.19 Human C-Type Lectins, MGL, DC-SIGN and Langerin, Their Interactions With Endogenous and Exogenous Ligand Patterns
		3.19.1. Introduction
		3.19.2. Expression and function of DC-SIGN, Langerin andMGL
		3.19.3. Carbohydrate specificities of the C-type lectins in host-pathogen interactions
			3.19.3.1. DC-SIGN
			3.19.3.2. Langerin
			3.19.3.3. MGL
		3.19.4. Endogenous interactions of the C-type lectins DC-SIGN, Langerin andMGL
			3.19.4.1. Endogenous ligands on immunecells
			3.19.4.2. Endogenous self and altered-self ligands on tissues
			3.19.4.3. Endogenous secretory/soluble ligands
		3.19.5. Glycan-modified antigens for improved DC targeting and induction of immunity
		3.19.6. Future directions
		Acknowledgment
		References
	3.20 Serum Anti-Carbohydrate Antibodies and Hyperacute Rejection
		3.20.1. Introduction
		3.20.2. ABO blood groups
			3.20.2.1. Structure and synthesis of ABH antigens
			3.20.2.2. Origin of antibodies against ABH antigens
			3.20.2.3. Sequence features and VDJ usage for anti-ABH antibodies
			3.20.2.4. Structure of anti-ABH antibodies
			3.20.2.5. Role of anti-ABH antibodies in hyperacute rejection
			3.20.2.6. Enzymatic conversion of type Aand Bblood to typeO
		3.20.3. Antibodies to non-blood group carbohydrates of relevance to xenotransplantation
			3.20.3.1. Structural basis for recognition of αGal by antibodies
			3.20.3.2. Progress with genetic engineering of pigs for xenotransplantation into humans
		3.20.4. Carbohydrate binding antibodies beyond transfusion or transplantation
			3.20.4.1. Role of αGal antibodies in red meat allergy
			3.20.4.2. ABO and αGal antibodies: Implications for infectious disease
		References
	3.21 Zwitterionic Polysaccharides in Immunity
		3.21.1. Introduction
			3.21.1.1. T-cell independent and dependent immune responses
		3.21.2. Types of zwitterionic polysaccharides
			3.21.2.1. ZPSs from Bacteroides fragilis
				3.21.2.1.1. PSA1
				3.21.2.1.2. PSB
			3.21.2.2. ZPS from Streptococcus pneumoniae:Sp1
		3.21.3. Biochemistry ofZPSs
			3.21.3.1. Structural characteristics
			3.21.3.2. MHCII dependent processing and presentation ofZPSs
		3.21.4. Chemical biology ofZPSs
			3.21.4.1. Functional group modifications ofZPSs
			3.21.4.2. Chemical synthesis of Morganella morganii O-chain antigen
			3.21.4.3. Chemical syntheses ofSp1
			3.21.4.4. Chemical syntheses of PSA1
		3.21.5. Applications of ZPSs in cancer and bacterial vaccines as carriers
			3.21.5.1. Use of ZPSs againstcancer
			3.21.5.2. Use of ZPSs as vaccines against bacteria
		3.21.6. Conclusion
		References
	3.22 Glycolipids as Antigens for Semi-Invariant Natural Killer TCells
		3.22.1. Introduction
		3.22.2. Structural variants of α-GalCer
			3.22.2.1. Ceramide modifications
			3.22.2.2. Glycolipids modified to inhibit glycoside hydrolysis
			3.22.2.3. Sugar modifications
		3.22.3. Natural antigens
			3.22.3.1. Exogenous natural antigens
			3.22.3.2. Endogenous natural antigens
		3.22.4. Conclusions
		References
	Back Cover
9780128222447_WEB04
	Front Cover
	Comprehensive Glycoscience
	Copyright
	Editor Biographies
		Editor-in-Chief
		Volume Editors
	List of Contributors for Volume 4
	Preface
	Contents of Volume 4
	Permission Acknowledgement
	4.01 Polysaccharides and Applications in Regenerative Medicine
		4.01.1. Introduction
		4.01.2. Physicochemical properties of polysaccharides for regenerative medicine
			4.01.2.1. Cellulose
			4.01.2.2. Chitin and chitosan
			4.01.2.3. Alginate
			4.01.2.4. Glycosaminoglycans
				4.01.2.4.1. Hyaluronicacid
			4.01.2.5. Other polysaccharides
		4.01.3. Tissue engineering applications
			4.01.3.1. Applications in bone and cartilage regenerative medicine
			4.01.3.2. Applications in cardiovascular regenerative medicine
			4.01.3.3. Neural tissue regeneration
			4.01.3.4. Skin tissue regeneration and wound healing
		4.01.4. Conclusions and future outlook
		References
	4.02 Polysaccharides for Drug Delivery: The Development of Polysaccharide-Based Materials and Glycopolymer to Improve Drug Del ...
		4.02.1. Introduction
		4.02.2. Classification of polysaccharides
			4.02.2.1. Linear polysaccharides
				4.02.2.1.1. Linear homo-polysaccharides
				4.02.2.1.2. Linear heteropolysaccharides
			4.02.2.2. Branched polysaccharides
			4.02.2.3. Complex polysaccharides
			4.02.2.4. Glycopolymers
		4.02.3. Design ofDDS
		4.02.4. Drug delivery applications
			4.02.4.1. Glycopolymers for DDS applications
				4.02.4.1.1. Nano (micro)gels
					4.02.4.1.1.1. AlginateDDS
					4.02.4.1.1.2. DextranDDS
					4.02.4.1.1.3. ChitosanDDS
					4.02.4.1.1.4. Chemically cross-linked hydrogel
					4.02.4.1.1.5. Photo-cross-linked hydrogel
					4.02.4.1.1.6. Interpenetrating polymer network (IPN) type hydrogels
					4.02.4.1.1.7. Non-covalent bond based hydrogel
				4.02.4.1.2. Polymeric micelles
				4.02.4.1.3. Polymeric vesicles
			4.02.4.2. Engineered natural polysaccharides forDDS
				4.02.4.2.1. Injectable hydrogels
				4.02.4.2.2. Cellulose nanocrystal electrospinning method for sustained release
				4.02.4.2.3. Microcapsules for sustained release
				4.02.4.2.4. pH Responsive platform
				4.02.4.2.5. Cellulose for oral drug delivery applications
		4.02.5. Conclusion
		References
	4.03 Cationic Polysaccharides and Glycopolymers in Gene Therapy
		4.03.1. Introduction
		4.03.2. Natural polysaccharides in gene delivery
			4.03.2.1. Chitosan and chitosan derivatives
			4.03.2.2. Cationic dextran derivatives
			4.03.2.3. Cationic cyclodextrins
			4.03.2.4. Quaternized cellulose
		4.03.3. Cationic glycopolymers in gene delivery
			4.03.3.1. Cationic glycopolymer synthesis
				4.03.3.1.1. Linear polymers
				4.03.3.1.2. Branched polymers
				4.03.3.1.3. Star polymers
				4.03.3.1.4. Graft copolymers
			4.03.3.2. Evaluation of cationic glycopolymers for gene delivery
				4.03.3.2.1. Effect of cationic charge
				4.03.3.2.2. Effect of amine groups
				4.03.3.2.3. Effect of polymer architecture
				4.03.3.2.4. Effect of molecular weight
				4.03.3.2.5. Effect of hydroxyl chemistry
			4.03.3.3. Glycosylation of cationic polymers
		4.03.4. Conclusion and future prospects
		References
	4.04 Hydrogels Based on Natural Polysaccharides and Their Applications
		4.04.1. Introduction
		4.04.2. Hydrogels
		4.04.3. Natural polysaccharides
			4.04.3.1. Chitosan
			4.04.3.2. Alginate
			4.04.3.3. Starch
			4.04.3.4. Cellulose
			4.04.3.5. Lignin
			4.04.3.6. Naturalgums
			4.04.3.7. Other natural polysaccharides
		4.04.4. Applications of hydrogels based on natural polysaccharides
			4.04.4.1. Biomedical applications
				4.04.4.1.1. Drug delivery
				4.04.4.1.2. Tissue engineering
				4.04.4.1.3. Wound dressing
				4.04.4.1.4. Ophthalmology
			4.04.4.2. Food industry applications
				4.04.4.2.1. Food packing
				4.04.4.2.2. Encapsulation and delivery
				4.04.4.2.3. Fat replacers
				4.04.4.2.4. Emulsion stabilization
			4.04.4.3. Agriculture
			4.04.4.4. Water treatment
			4.04.4.5. Supercapacitors
			4.04.4.6. Biosensors
			4.04.4.7. Hygiene and cosmetic products
			4.04.4.8. Enhanced oil recovery
		4.04.5. The future of hydrogels based on natural polysaccharides
		References
	4.05 Glycopolymer-Based Hydrogels, Microgels, and Nanogels and Their Applications
		4.05.1. Introduction
		4.05.2. Glycopolymer hydrogels based on the dynamic covalent bond between phenylboronic acid and carbohydrates
		4.05.3. Glycopolymer hydrogel based on carbohydrate-metal ion interaction
		4.05.4. Glycopolymer hydrogel based on carbohydrate-protein interaction
		4.05.5. Glycopolymer hydrogel based on carbohydrate crosslinker
		4.05.6. The application of glycopolymer hydrogel in protein stabilization
		4.05.7. The application of glycopolymer hydrogel in cell proliferation
		4.05.8. The application of glycopolymer hydrogel in receptor-targeting
		4.05.9. The application of glycopolymer hydrogel in drug delivery
		4.05.10. The application of glycopolymer hydrogel as heavy metal adsorbent
		References
	4.06 Glycan Arrays: Construction, Detection, and Analysis
		4.06.1. Introduction
		4.06.2. Glycan array construction
			4.06.2.1. Array components and diversity
				4.06.2.1.1. Glycan sources
				4.06.2.1.2. Size ofarray
				4.06.2.1.3. Controls and non-glycan components
				4.06.2.1.4. Glycan presentation
			4.06.2.2. Immobilization methods
				4.06.2.2.1. Noncovalent methods
				4.06.2.2.2. Covalent methods
				4.06.2.2.3. Robotic printing technology
				4.06.2.2.4. Bead, NGS and cell based array technologies
		4.06.3. Assay
		4.06.4. Detection strategies
			4.06.4.1. Fluorescence based detection
			4.06.4.2. Mass spectrometry based detection
			4.06.4.3. Surface plasmon resonance based detection
			4.06.4.4. Other methods of detection
			4.06.4.5. Detection instrumentation
		4.06.5. Analysis
			4.06.5.1. Analysis consideration for fluorescencedata
			4.06.5.2. Analysis considerations of other methods
		4.06.6. Conclusions
		Acknowledgment
		References
	4.07 Application of Glycan-Related Microarrays
		4.07.1. Introduction
			4.07.1.1. Background and scope of the chapter
			4.07.1.2. Glycan microarrays(GMA)
			4.07.1.3. Lectin microarray(LMA)
		4.07.2. Applications of glycan microarrays
			4.07.2.1. Microbiology
			4.07.2.2. Influenza viruses
			4.07.2.3. Immunology and cell signaling
			4.07.2.4. Serum anti-glycan antibodies and cancer biology
		4.07.3. Future perspectives of glycan microarray
		4.07.4. Principle of lectin microarrays
			4.07.4.1. Lectin sources
			4.07.4.2. Fabrication of lectin microarrays
			4.07.4.3. Labeling of glycoconjugates
			4.07.4.4. Detection of lectin-carbohydrate interactions
			4.07.4.5. Availability of lectin microarray platforms
		4.07.5. Applications of lectin microarrays for glycomic profiling
			4.07.5.1. Cells
			4.07.5.2. Microorganisms
			4.07.5.3. Extracellular vesicles
			4.07.5.4. Body fluids
			4.07.5.5. Tissues
			4.07.5.6. Endogenous glycoproteins
			4.07.5.7. Recombinant glycoproteins
		4.07.6. Conclusion and perspectives for lectin microarray
		References
		Relevant Websites
	4.08 Carbohydrate Biosensors and Applications
		4.08.1. Introduction
		4.08.2. Construction of carbohydrate biosensors
			4.08.2.1. Biosensor surface topology
			4.08.2.2. Time and cost factors
		4.08.3. Nanomaterials in carbohydrate biosensors
			4.08.3.1. Metal nanoparticles
			4.08.3.2. Carbon nanomaterials
			4.08.3.3. Silicon nanomaterials
			4.08.3.4. Cellulose nanomaterials
		4.08.4. Detection methods
			4.08.4.1. Cross-linking reactions
			4.08.4.2. Biotin-Avidin
			4.08.4.3. Click chemistry
			4.08.4.4. Glycopeptides
		4.08.5. Label-free techniques
			4.08.5.1. Surface plasmon resonance (SPR) and local SPR(LSPR)
			4.08.5.2. Atomic force microscopy
			4.08.5.3. Field-effect transistor(FET)
			4.08.5.4. Electrochemical impedance spectroscopy(EIS)
			4.08.5.5. Surface stress-based detection
		4.08.6. Conclusion
		References
	4.09 Microbial Glycan Arrays
		4.09.1. Introduction
		4.09.2. Access to microbial glycans for glycan arrays
		4.09.3. Microbial glycan arrays and their applications
			4.09.3.1. Arrays containing a broad range of microbial glycans
				4.09.3.1.1. Consortium for Functional Glycomics pathogenarray
				4.09.3.1.2. Max Planck microbial glycanarray
				4.09.3.1.3. Imperial College glucanarray
			4.09.3.2. Focused microbial glycan arrays
				4.09.3.2.1. Salmonella O-antigenarray
				4.09.3.2.2. Mycobacterial cell wall glycanarray
				4.09.3.2.3. Arrays of Bacillus anthracis exosporium glycans
				4.09.3.2.4. Glycophosphosphatidyl-inositol containing parasite glycan arrays
				4.09.3.2.5. Schistosome arrays
				4.09.3.2.6. Clostridium difficile oligosaccharidearray
				4.09.3.2.7. Cryptococcus neoformansarray
		4.09.4. Future directions
		References
	4.10 Synthesis, Characterization and Applications of Glycopolymers
		4.10.1. Introduction on glycopolymers
		4.10.2. Synthesis of glycopolymers
			4.10.2.1. Free-radical polymerization
			4.10.2.2. Ring opening metathesis polymerization
			4.10.2.3. Nitroxide mediated polymerization(NMP)
			4.10.2.4. Cu-based controlled living radical polymerizations
				4.10.2.4.1. Atom transfer radical polymerization
				4.10.2.4.2. Single electron transfer radical living polymerization
			4.10.2.5. Reversible addition fragmentation chain transfer polymerization
			4.10.2.6. Ionic polymerization
			4.10.2.7. Post-polymerization modification reactions
				4.10.2.7.1. Cu-catalyzed azide-alkyne cycloaddition(CuAAC)
				4.10.2.7.2. Thiol-ene reaction
			4.10.2.8. Applications of glycopolymers
				4.10.2.8.1. Pathogen inhibition
					4.10.2.8.1.1. Influenza viruses
					4.10.2.8.1.2. Bacteria inhibition
					4.10.2.8.1.3. HIV inhibition
				4.10.2.8.2. Biosensing and bioimaging
				4.10.2.8.3. Gene delivery
				4.10.2.8.4. Cancer therapy
			4.10.2.9. Conclusion
		References
	4.11 Glycopolymer Functionalized Nanoparticles and Their Applications
		4.11.1. Introduction
		4.11.2. Synthesis of glycopolymer-functionalized nanoparticles
			4.11.2.1. Self-assembly of amphiphilic glycopolymers
				4.11.2.1.1. Micelles
				4.11.2.1.2. Polymersomes, hollow nanoparticles and other morphologies
			4.11.2.2. Conjugation of glycopolymers with (in)organic nanoparticles
				4.11.2.2.1. Glycopolymer-functionalized gold and silver nanoparticles
				4.11.2.2.2. Glycopolymer-functionalized iron oxide nanoparticles
				4.11.2.2.3. Glycopolymer-functionalized carbon-based nanoparticles
				4.11.2.2.4. Glycopolymer-functionalized silica nanoparticles
				4.11.2.2.5. Glycopolymer-functionalized polystyrene nanoparticles
		4.11.3. Application of glycopolymer-functionalized nanoparticles
			4.11.3.1. Protein recognition and conjugation
			4.11.3.2. Antimicrobial agents
			4.11.3.3. Cancer therapy
			4.11.3.4. Bio-mimetic models
			4.11.3.5. Drug and gene delivery
			4.11.3.6. Cellular imaging
		4.11.4. Conclusion
		References
	4.12 Glycopolymer Conjugates: Preparation and Functions
		4.12.1. Introduction
		4.12.2. Glycopolymer conjugation to solid substrates
			4.12.2.1. Glycopolymer conjugate with substrate by polymer coating
			4.12.2.2. Glycopolymer brush by ``grafting from´´method
			4.12.2.3. Glycopolymer conjugates by ``grafting to´´method
			4.12.2.4. Glycopolymer-gold substrate conjugates
			4.12.2.5. Glycopolymer arrays
		4.12.3. Glycopolymer-nanomaterials conjugate
			4.12.3.1. Glycopolymer-metal nanoparticle conjugates
			4.12.3.2. Other glycopolymer-nanomaterial conjugates
		4.12.4. Glycopolymer conjugate with living organisms
		4.12.5. Conclusion
		References
	4.13 Glycoclusters and Glycodendrimers
		4.13.1. Introduction
		4.13.2. Scaffolds
			4.13.2.1. Small molecular scaffolds
			4.13.2.2. Macrocyclic scaffolds
				4.13.2.2.1. Cyclodextrins
				4.13.2.2.2. Calix[n]arenes
				4.13.2.2.3. Pillar[n]arene
				4.13.2.2.4. Cucurbit[n]urils
				4.13.2.2.5. Cyclopeptides
				4.13.2.2.6. Buckminsterfullerene(C60)
				4.13.2.2.7. Oligosilsesquioxanes
				4.13.2.2.8. Cyclams and porphyrins
			4.13.2.3. Metalloglycoconjugates
		4.13.3. Applications
			4.13.3.1. Lectins
			4.13.3.2. Enzyme inhibition
				4.13.3.2.1. Deoxynojirimycin
				4.13.3.2.2. Other iminosugar inhibitors
				4.13.3.2.3. Heteroglycocluster effects
			4.13.3.3. Targeting bacterial toxins
			4.13.3.4. Glycoconjugate vaccines
			4.13.3.5. Gene delivery
		4.13.4. Conclusion
		References
	4.14 Surface Immobilized Glycopolymers
		4.14.1. Introduction
		4.14.2. Synthesis of glycopolymer immobilized surfaces
			4.14.2.1. Top down strategy: Grafting tomethod
			4.14.2.2. Thiol-gold or silane coupling
				4.14.2.2.1. Grafting onto amine and hydroxyl functionalized surfaces
				4.14.2.2.2. Catechol-based adhesion
				4.14.2.2.3. Layer by layer (LBL) assembledfilms
			4.14.2.3. Bottom up strategy: ``Graftingfrom´´
				4.14.2.3.1. Conventional free radical polymerization on surface
				4.14.2.3.2. Control/living radical polymerization on surface
			4.14.2.4. Immobilization of vinyl groups onto surfaces and the immobilization of glycopolymers on surface via ``grafting  ...
		4.14.3. Applications of glycopolymer immobilized surfaces
			4.14.3.1. Interaction with proteins
			4.14.3.2. Interaction with bacteria andcells
			4.14.3.3. Other applications
		4.14.4. Summary
		References
	4.15 Carbohydrate Functionalized Liposomes and Applications
		4.15.1. Introduction
		4.15.2. Preparations and characterization of carbohydrate functionalized liposomes
		4.15.3. Biomedical applications of carbohydrate functionalized liposomes
			4.15.3.1. Carbohydrate functionalized liposomes for targeted delivery of antigens, drugs, andgenes
				4.15.3.1.1. Galactosylated liposomes
				4.15.3.1.2. Mannosylated liposomes
				4.15.3.1.3. Sialylated liposomes
				4.15.3.1.4. LeX-liposomes
				4.15.3.1.5. Fucosylated liposomes
			4.15.3.2. Carbohydrate functionalized liposomes as biomimetic multivalent ligands
			4.15.3.3. Carbohydrate functionalized liposomes as enzyme substrates and inhibitors
			4.15.3.4. Carbohydrate functionalized liposomes as biosensors and microarrays
			4.15.3.5. Carbohydrate functionalized liposomes for cell surface re-engineering
		4.15.4. Summary and future perspective
		Acknowledgment
		References
	4.16 Carbohydrate-Presenting Metal Nanoparticles: Synthesis, Characterization and Applications
		4.16.1. Introduction
			4.16.1.1. Metal glyconanoparticles
			4.16.1.2. Magnetic/paramagnetic property ofMNPs
			4.16.1.3. Localized surface plasmon resonance inMNPs
			4.16.1.4. Luminescence and fluorescence inMNPs
			4.16.1.5. Near-infrared absorption and light-to-heat energy transformations
		4.16.2. Synthesis of carbohydrate-presenting metal nanoparticles
			4.16.2.1. Non-covalent attachment
			4.16.2.2. Covalent conjugation
				4.16.2.2.1. Synthesis of glyco-AuNPs by direct conjugation
					4.16.2.2.1.1. Method i-One-pot synthesis with a reducingagent
					4.16.2.2.1.2. Method ii-One-pot synthesis without additional reducingagent
					4.16.2.2.1.3. Method iii-Ligand exchange
				4.16.2.2.2. Synthesis of other glyco-MNPs by direct conjugation
					4.16.2.2.2.1. Glyco-AgNPs
					4.16.2.2.2.2. Glyco-iron oxide nanoparticles
					4.16.2.2.2.3. Other glyco-MNPs
				4.16.2.2.3. Synthesis of glyco-AuNPs by post-modification
		4.16.3. Characterization of carbohydrate-presenting metal nanoparticles
			4.16.3.1. Composition
				4.16.3.1.1. NMR
				4.16.3.1.2. IR
				4.16.3.1.3. XPS
			4.16.3.2. Particle size, shape and surface charge
			4.16.3.3. Ligand density
				4.16.3.3.1. Anthrone/phenol sulfuric acid colorimetricassay
				4.16.3.3.2. TGA
				4.16.3.3.3. NMR
			4.16.3.4. Binding affinity
				4.16.3.4.1. Fluorescence
				4.16.3.4.2. ITC
				4.16.3.4.3. SPR
				4.16.3.4.4. QCM
				4.16.3.4.5. DLS
		4.16.4. Applications of carbohydrate-modified metal nanoparticles
			4.16.4.1. Lectin sensing
			4.16.4.2. Sensing/imaging mammalian cells, bacteria and viruses
			4.16.4.3. Invivo sensing/imaging
				4.16.4.3.1. Magnetic resonance imaging(MRI)
				4.16.4.3.2. Positron emission tomography(PET)
			4.16.4.4. Antitumor and antimicrobial glyco-MNPs
			4.16.4.5. Glyco-MNP vaccines
		4.16.5. Summary and conclusions
		Acknowledgment
		References
	4.17 Carbohydrate Modified Non-Metallic Nanomaterials and Their Application Against Infectious Diseases
		4.17.1. Introduction
		4.17.2. Nanocarriers used in drug delivery systems
			4.17.2.1. Advantages of nanoparticle-basedDDS
			4.17.2.2. Preparation and application of nanoparticles inDDS
		4.17.3. Carbohydrate modified non-metallic nanoparticles (CMNs) and their advantages
			4.17.3.1. Carbohydrates used to prepare non-metallic nanoparticles
			4.17.3.2. Preparation methods ofCMNs
				4.17.3.2.1. Covalently crosslinkedCMNs
				4.17.3.2.2. Ionically crosslinkedCMNs
				4.17.3.2.3. CMNs by polyelectrolyte complexation(PEC)
				4.17.3.2.4. Self-assembledCMNs
				4.17.3.2.5. CMNs obtained by copolymerization
					4.17.3.2.5.1. CMNs by radical polymerization
				4.17.3.2.6. CMNs from preformed copolymer
				4.17.3.2.7. CMNs developed via nanoprecipitation
		4.17.4. Biomedical application ofCMNs
			4.17.4.1. Bacterial infectious diseases
				4.17.4.1.1. Tuberculosis
				4.17.4.1.2. Salmonellosis
				4.17.4.1.3. Staphylococcus aureus
			4.17.4.2. Protozoan infectious diseases
			4.17.4.3. Viral infectious diseases
			4.17.4.4. Fungal infections
		4.17.5. Future perspective ofCMNs
		4.17.6. Concluding remarks
		References
	4.18 Carbohydrate Functionalized Quantum Dots in Sensing, Imaging and Therapy Applications
		4.18.1. Introduction
		4.18.2. Quantumdots
			4.18.2.1. The discovery of semiconductor quantumdots
			4.18.2.2. Semiconductor quantum dots: general features and synthesis
			4.18.2.3. Glyco-quantum dots synthesis
		4.18.3. Glyco-QDs in bioimaging, sensing, diagnosis and therapy
			4.18.3.1. Glyco-QDs in bioimaging
			4.18.3.2. Glyco-QDs in sensing applications
			4.18.3.3. Glyco-QDs: Update and perspective in diagnostic and therapeutic applications
		Acknowledgment
		References
	4.19 Nanostructured Materials for Glycan Based Applications
		4.19.1. Introduction
		4.19.2. Glycan-based applications of gold nanostructures
			4.19.2.1. Nanoparticle synthesis
			4.19.2.2. Gold nanoparticles and biomolecular recognition
			4.19.2.3. Application of glycan-modified gold nanoparticles in cancer treatment
			4.19.2.4. HIV and virus-related applications of glycan-modified gold nanoparticles
			4.19.2.5. Interactions of glycan-modified gold nanoparticles with bacteria
			4.19.2.6. Applications of glycan-modified gold nanoparticles to imaging
		4.19.3. Glycan-based applications of quantumdots
			4.19.3.1. Cyclodextrin-conjugatedQDs
				4.19.3.1.1. Sensing of organic molecules
				4.19.3.1.2. Delivering therapeutics
			4.19.3.2. Hyaluronic acid-conjugatedQDs
				4.19.3.2.1. Imaging invivo
				4.19.3.2.2. Theranostics
				4.19.3.2.3. Hyaluronidase (HAase) detection
			4.19.3.3. Sialic acid-terminated oligosaccharides-conjugatedQDs
			4.19.3.4. Lectin-conjugatedQDs
			4.19.3.5. Phenylboronic acid-conjugatedQDs
			4.19.3.6. Monosaccharides-imprintedQDs
			4.19.3.7. Monosaccharides-immobilizedQDs
			4.19.3.8. Future challenges
		4.19.4. Magnetic nanoparticles
		4.19.5. Mesoporous nanoparticles
			4.19.5.1. Enrichment of glycopeptides and glycans
			4.19.5.2. Drug delivery
			4.19.5.3. Carbohydrate/glycan-functionalized mesoporous materials
			4.19.5.4. Carbohydrate/glycan targeting mesoporous materials
			4.19.5.5. Glycans as a stimulus
		4.19.6. Carbon nanomaterials
			4.19.6.1. Fullerenes and glycans
			4.19.6.2. Carbon nanotubes and glycans
			4.19.6.3. Graphene and glycans
		4.19.7. Nanofibers
		4.19.8. Core-shell nanoparticles
		4.19.9. Conclusions
		References
	4.20 Nanocellulose: Preparation, Functionalization and Applications
		4.20.1. Introduction
		4.20.2. Main classes of nanocellulose, properties and sources
		4.20.3. Preparation/isolation methods of nanocellulose
		4.20.4. Functionalization of nanocellulose
			4.20.4.1. Covalent and non-covalent functionalization of nanocellulose
			4.20.4.2. Characterization methods of functionalized nanocellulose
		4.20.5. Applications of nanocellulose
			4.20.5.1. Nanocellulose as reinforcement materials
			4.20.5.2. Medical applications
				4.20.5.2.1. Tissue engineering and wound healing
				4.20.5.2.2. Drug delivery
				4.20.5.2.3. (Bio)sensing
				4.20.5.2.4. Other medical applications
			4.20.5.3. Water purification
			4.20.5.4. Catalysis
			4.20.5.5. Other applications
		4.20.6. Conclusions and outlook
		References
	4.21 Profiling Carbohydrate-Protein Interaction Using Nanotechnology
		4.21.1. Introduction
		4.21.2. Inorganic nanostructures
			4.21.2.1. Gold and silver nanoparticles
			4.21.2.2. Magnetic nanoparticles
			4.21.2.3. Quantumdots
			4.21.2.4. Silica nanoparticles
			4.21.2.5. Upconversion nanoparticles
		4.21.3. Carbon based nanomaterials
			4.21.3.1. Fullerenes
			4.21.3.2. Carbon nanotubes
			4.21.3.3. Graphene and carbon quantumdots
		4.21.4. Polysaccharide nanoparticles
			4.21.4.1. Chitosan nanoparticles
			4.21.4.2. Hyaluronic acid nanoparticle
			4.21.4.3. Dextran and starch nanoparticles
		4.21.5. Glyconanomaterials for diagnosis and biomedical applications
		4.21.6. Lectin functionalized nanomaterials
		4.21.7. Conclusion
		References
	4.22 Glyco-Nanomedicines and Their Applications in Cancer Treatment
		4.22.1. Introduction
		4.22.2. Types of anticancer nanomedicines in clinical settings
		4.22.3. Gene delivery
			4.22.3.1. siRNA and cancer therapy
		4.22.4. Design characteristics of vectors in nanomedicine
		4.22.5. Glycopolymer-targeted delivery of genes and chemotherapeutic agents
		4.22.6. Stimuli-responsive gene delivery systems
		4.22.7. Stimuli-responsive drug delivery systems
		4.22.8. Nanotheranostics compounds
		4.22.9. Nanoparticle-based combination therapy of drugs andgenes
		4.22.10. Polymer conjugates
		4.22.11. Successful delivery/application: Future potential candidates
		4.22.12. What are the challenges, loopholes and how to overcome?
		4.22.13. Conclusion
		References
	Back Cover
9780128222447_WEB05
	Front Cover
	Comprehensive Glycoscience
	Copyright
	Editor Biographies
		Editor-in-Chief
		Volume Editors
	List of Contributors for Volume 5
	Preface
	Contents of Volume 5
	Permission Acknowledgement
	5.01 Drosophila melanogaster in Glycobiology: Their Mutants Are Excellent Models for Human Diseases
		5.01.1. Introduction
			5.01.1.1. Normal development in Drosophila
			5.01.1.2. Drosophila mutagenesis
				5.01.1.2.1. An overview of Drosophila mutagenesis
				5.01.1.2.2. RNA interference
					5.01.1.2.2.1. The mechanism of RNA interference
					5.01.1.2.2.2. Using the Drosophila RNAi system for gene function analyses
				5.01.1.2.3. Genome editing by CRISPR/Cas9 system11,12
		5.01.2. Genome-wide screening and analysis of glycan functions in Drosophila melanogaster
		5.01.3. N-Glycans in Drosophila melanogaster
			5.01.3.1. The structure and biosynthetic pathway of N-Glycans
			5.01.3.2. The glycosyltransferases and glycosidases in N-glycan synthesis
			5.01.3.3. The function of N-Glycans
		5.01.4. O-Glycans in Drosophila melanogaster
			5.01.4.1. Mucin-type Glycans in Drosophila melanogaster
				5.01.4.1.1. The structures and glycosyltransferases of mucin-type glycans
				5.01.4.1.2. The function of mucin-type glycans
			5.01.4.2. Proteoglycans in Drosophila melanogaster
				5.01.4.2.1. The structure of proteoglycans
				5.01.4.2.2. The biosynthetic pathway of GAGs and the glycosyltransferases and sulfotransferases involved in this pathway
				5.01.4.2.3. The core proteins of proteoglycans
				5.01.4.2.4. The function of proteoglycans
			5.01.4.3. O-Mannosylglycan in Drosophila melanogaster
				5.01.4.3.1. The glycosyltransferases and other enzymes in O-mannosylglycan synthesis
				5.01.4.3.2. The function of O-mannosylglycan
			5.01.4.4. O-GlcNAc in Drosophila melanogaster
				5.01.4.4.1. The glycosyltransferases and glycosidase in O-GlcNAc modification
				5.01.4.4.2. The function of O-GlcNAc modification in the cytosol and nucleus
			5.01.4.5. O-glycans on Notch receptor
				5.01.4.5.1. The glycosyltransferases in O-glycan synthesis on the Notch receptor
				5.01.4.5.2. Function of O-glycan synthesis on Notch receptor
			5.01.4.6. O-fucosylation on other proteins
		5.01.5. Glycolipids in Drosophila melanogaster
			5.01.5.1. The structure of glycolipids in the biosynthetic pathway of glycolipids
			5.01.5.2. The function of glycolipids
		5.01.6. Sugar-nucleotide transporters in Drosophila melanogaster
			5.01.6.1. An overview of the sugar-nucleotide transporter family
			5.01.6.2. Function ofSNTs
		5.01.7. Lectins in Drosophila melanogaster
			5.01.7.1. Overview of the lectin family
			5.01.7.2. Function of lectins
		5.01.8. Conclusions and future perspectives
		References
	5.02 Glycobiology of Caenorhabditis elegans
		5.02.1. Introduction
		5.02.2. GlcNAcβ1-N-Asn linked N-glycans
			5.02.2.1. Structures of N-glycans
			5.02.2.2. Initial stages of N-glycan synthesis are conserved but the final stages arenovel
			5.02.2.3. Functions of N-glycans
		5.02.3. GalNAcα1-O-Ser/Thr linked O-glycans
		5.02.4. Xylβ1-O-Ser linked O-glycans: Glycosaminoglycans/proteoglycans
			5.02.4.1. Glycosaminoglycans
			5.02.4.2. Chondroitin and squashed vulva (sqv)genes
			5.02.4.3. Heparan polymerization and sulfation
		5.02.5. Cytoplasmic and nuclear O-glycosylation
		5.02.6. Other O-glycan modifications of extracellular proteins
		5.02.7. Glycosphingolipids and glycosylphosphatidylinositol anchors
		5.02.8. Biosynthesis of fucosylated and galactosylated glycans
		5.02.9. Chitin and other polysaccharides
		5.02.10. Donors for glycan biosynthesis
			5.02.10.1. Nucleotide sugar biosynthesis
			5.02.10.2. Nucleotide sugar transport
			5.02.10.3. Lumenal nucleoside diphosphatases
		5.02.11. Endogenous lectins in C.elegans
		5.02.12. Resistance of C.elegans mutants to toxins, lectins and bacteria
		5.02.13. Concluding remarks
		References
		Relevant Websites
	5.03 Glycobiology of Yeast: Applications to Glycoprotein Expression and Remodeling
		5.03.1. Overview of glycans inyeast
			5.03.1.1. Contributions of yeast research: Genetic methods
			5.03.1.2. Glycan structures of yeast glycoproteins
			5.03.1.3. Sphingolipids ofyeast
		5.03.2. Synthesis of N- and O-glycans in S.cerevisiae
			5.03.2.1. N-Glycans
			5.03.2.2. O-Glycans
			5.03.2.3. Localization mechanism of mannosyltransferases in theGolgi
			5.03.2.4. Metabolism of mannose donors
			5.03.2.5. Degradation of glycoproteins
		5.03.3. Remodeling of yeast glycans
			5.03.3.1. Remodeling of N-glycans to complex-type
			5.03.3.2. Remodeling of N-glycans to mannose-6-phosphate-type
			5.03.3.3. Remodeling of O-glycans inyeast
			5.03.3.4. Remodeling of N-glycans by endo-β-N-acetylglucosaminidase
			5.03.3.5. Perspectives
		5.03.4. Modification by glycosylphosphatidylinositol
			5.03.4.1. Synthesis of GPI precursor and its transfer to proteins
			5.03.4.2. GPI transamidase
			5.03.4.3. Inositol deacylation
			5.03.4.4. Lipid remodeling
			5.03.4.5. Glycan remodeling and ERexit
			5.03.4.6. Further modification of GPI and targeting to the cell surface
			5.03.4.7. Relationship between lipid moiety of GPI-APs and their final destination
			5.03.4.8. Other biological phenomena involving GPI anchors
		5.03.5. Concluding remarks
		References
	5.04 Lectin Repertoires in Invertebrates and Ectothermic Vertebrates: Structural and Functional Aspects
		5.04.1. Introduction
		5.04.2. Animal model systems for the study of lectins
		5.04.3. Current approaches for assessing the structural and functional diversity of lectin repertoires
		5.04.4. Biochemical, structural, and functional aspects of lectins from invertebrates and ectothermic vertebrates
			5.04.4.1. C-type lectins
				5.04.4.1.1. The CTLDfold
				5.04.4.1.2. Calcium-bindingsites
				5.04.4.1.3. CTLD-carbohydrate interactions
			5.04.4.2. Galectins
				5.04.4.2.1. Proto-type galectins are structurally conserved in ectothermic vertebrates
				5.04.4.2.2. Unique features of galectins from invertebrates and protochordates
			5.04.4.3. F-type lectins
				5.04.4.3.1. The F-type lectin family
				5.04.4.3.2. Sequence variants of the F-typeCRD
				5.04.4.3.3. Phylogeny of the F-typefold
			5.04.4.4. R-type lectins(RTLs)
			5.04.4.5. Pentraxins
			5.04.4.6. Calnexin and calreticulin
			5.04.4.7. Novel lectin families identified in teleosts
				5.04.4.7.1. Rhamnose-binding lectins
				5.04.4.7.2. Pufflectins
		5.04.5. Conclusions
		Acknowledgment
		References
	5.05 Structure and Biological Functions of Plant Glycans and Polysaccharides
		5.05.1. Introduction of plant polysaccharides
			5.05.1.1. Cellulose
			5.05.1.2. Hemicellulose
			5.05.1.3. Pectin
			5.05.1.4. Storage polysaccharide
		5.05.2. Structure and function of plant polysaccharides
			5.05.2.1. Hemicellulose
			5.05.2.2. (13)-β-d-glucans
			5.05.2.3. Pectin (groupC)
				5.05.2.3.1. Arabinan
				5.05.2.3.2. Arabinogalactan
					5.05.2.3.2.1. AG derived from larch tree (Larix species)
					5.05.2.3.2.2. Activation of natural killer (NK)cells
					5.05.2.3.2.3. Gut microbiome
					5.05.2.3.2.4. Cold infection
				5.05.2.3.3. Astragalus mongholicus side chains of (13,6)-β-d-galactans
					5.05.2.3.3.1. Arabinogalactan from Angelica acutiloba
					5.05.2.3.3.2. Polysaccharides from Eclipta prostrata
			5.05.2.4. Storage polysaccharides for food raw materials18
				5.05.2.4.1. D-1: Inulin18
				5.05.2.4.2. D-2: Starch
				5.05.2.4.3. D-3: Chitin and chitosan
				5.05.2.4.4. D-4; Carrageenan
		5.05.3. Plant N-glycosylation
			5.05.3.1. Posttranslational modification of protein, glycosylation
			5.05.3.2. Protein N-glycosylation
			5.05.3.3. N-glycan biosynthesis in the ER and N-glycan\'s role in quality control
			5.05.3.4. Intracellular functions of N-glycans
			5.05.3.5. N-glycan maturation inGolgi
			5.05.3.6. Effects of sugar residues on N-glycan
			5.05.3.7. Plant N-glycosylation
		5.05.4. Immunogenicity of plant glycans and glycoengineering
			5.05.4.1. Immunogenicity of plant glycans
			5.05.4.2. Adjuvant effects of plant polysaccharides
			5.05.4.3. Glycoengineering of N-glycan in plants
			5.05.4.4. Glycoengineering of O-glycan in plants
		5.05.5. Concluding remarks
		References
	5.06 Glycan-Mediated Interactions Between Fungal and Higher AnimalCells
		5.06.1. Introduction
		5.06.2. Biosynthesis of cell wall polysaccharides in Aspergillus fumigatus
		5.06.3. β-1,3-Glucan
		5.06.4. Chitin
		5.06.5. α-1,3-Glucan
		5.06.6. β-1,3-/β-1,4-Glucan
		5.06.7. Galactosaminogalactan
		5.06.8. Galactomannan
		5.06.9. Biosynthesis of cell wall polysaccharides in Candida albicans
		5.06.10. β-1,2-Linked mannosylation of glycans in C.albicans
		5.06.11. Role of C.albicans pseudohyphal growth in virulence
		5.06.12. Recognition of fungi by hostcells
			5.06.12.1. Toll-like receptors
			5.06.12.2. C-type lectin receptors
		5.06.13. Conclusions and perspectives
		References
	5.07 Glycation in Disease
		5.07.1. Introduction
		5.07.2. Chemistry of protein glycation
		5.07.3. Protein glycation invivo
		5.07.4. The mechanisms of glycation-related pathogenesis
			5.07.4.1. Impairment of protein function by glycation
			5.07.4.2. Elevation of oxidative stress and carbonyl stress by glycation
			5.07.4.3. Activation of signal transduction by glycation
		5.07.5. Protein glycation and diseases
			5.07.5.1. Diabetic nephropathy
			5.07.5.2. Diabetic retinopathy
			5.07.5.3. Diabetic cataracts
			5.07.5.4. Diabetic neuropathy
			5.07.5.5. Diabetic atherosclerosis
			5.07.5.6. Neurodegenerative disease
		5.07.6. Enzymes that act on intermediate products of glycation
			5.07.6.1. Enzymes that act on the Amadori products (deglycating enzymes)
			5.07.6.2. Enzymes that act on di-carbonyl compounds
		5.07.7. Glycation inhibitors
		5.07.8. Concluding remarks
		References
	5.08 O-GlcNAcylation and Diabetes
		5.08.1. Introduction
		5.08.2. Roles of O-GlcNAcylation in diabetes
		5.08.3. The roles of OGT and OGA in the diabetes
			5.08.3.1. Enzymes controlling O-GlcNAc cycling
			5.08.3.2. O-GlcNAc Transferase
			5.08.3.3. O-GlcNAcase
		5.08.4. O-GlcNAc and the pathophysiology of diabetic organs
			5.08.4.1. Contribution of O-GlcNAc to the deleterious effect of diabetes on the pancreatic islets of Langerhans
			5.08.4.2. Contribution of O-GlcNAcylation to the deleterious effect of diabetes on theliver
			5.08.4.3. Contribution of O-GlcNAcylation to the deleterious effect of diabetes on adipose tissue and muscle tissue
			5.08.4.4. Contribution of O-GlcNAcylation to the deleterious effect of diabetes on theskin
		5.08.5. The role of O-GlcNAcylation in diabetic complications
			5.08.5.1. Contribution of O-GlcNAcylation to diabetic complications in theeyes
			5.08.5.2. Contribution of O-GlcNAcylation to diabetic nephropathy
			5.08.5.3. Contribution of O-GlcNAcylation to diabetic neuropathy
			5.08.5.4. Contribution of O-GlcNAcylation to cardiovascular complications in diabetes
		5.08.6. Concluding remarks and future directions
		References
		Relevant Websites
	5.09 Mammalian Cytosolic Galectins Act as Damage-Associated Molecular Patterns, Resolution-Associated Molecular Patterns, and ...
		5.09.1. Introduction
		5.09.2. Galectins are β-galactoside binding proteins involved in fuzzy interactions as drivers of liquid-liquid phase sep ...
		5.09.3. Galectins interact with glycan ligands attached to membrane proteins
		5.09.4. Some galectins are expressed ubiquitously in various organs and cells, and are involved in the innate immune resp ...
		5.09.5. Galectins are cytosolic lectins
		5.09.6. Galectins are released into the extracellular spaces by active secretion via a leaderless secretory pathway and b ...
		5.09.7. Some galectins, such as galectin-3 and -9, exert their activities as DAMPs to initiate proinflammatory responses
		5.09.8. Galectins also act as RAMPs in innate immunity
		5.09.9. Galectins act as extracellular soluble PRRs for PAMPs/MAMPs in innate immunity
		5.09.10. Galectins act as cytosolic PRRs for DAMPs in innate immunity
		5.09.11. Galectins interact with their ligands/receptors through three differentmodes
		5.09.12. Perspective
		Acknowledgment
		References
	5.10 Glycoconjugates for Adjuvants and Self-Adjuvanting Vaccines
		5.10.1. Introduction
		5.10.2. FDA approved adjuvants and development of lipid Aadjuvants
			5.10.2.1. Biofunctional studies of lipopolysaccharide and lipidA
			5.10.2.2. Lipid Astudies for structure-activity relationship and adjuvant development
			5.10.2.3. Self-adjuvanting vaccines
			5.10.2.4. TLR2 ligand-conjugated vaccines
		5.10.3. TLR4 ligand-conjugated vaccines
		5.10.4. CD1d ligand-conjugated vaccines
		5.10.5. Self-assembling self-adjuvanting vaccines
		5.10.6. Conclusion and outlook
		References
	5.11 C-Type Lectins and Their Roles in Disease and Immune Homeostasis
		5.11.1. Introduction and classification of C-type lectins
			5.11.1.1. Natural killer cell receptors
				5.11.1.1.1. Ly49
				5.11.1.1.2. NKG2
				5.11.1.1.3. LOX-1
			5.11.1.2. Asialoglycoprotein receptors
			5.11.1.3. Collectins
				5.11.1.3.1. MBL
				5.11.1.3.2. Conglutinin
				5.11.1.3.3. CL
				5.11.1.3.4. SP
			5.11.1.4. Selectins
			5.11.1.5. Myeloid C-type lectin receptors
				5.11.1.5.1. ITAM-bearing receptors
					5.11.1.5.1.1. Mincle/MCL
					5.11.1.5.1.2. Dectin-2
				5.11.1.5.2. HemITAM-bearing receptors
					5.11.1.5.2.1. Dectin-1
					5.11.1.5.2.2. DNGR-1
					5.11.1.5.2.3. SIGNR3
				5.11.1.5.3. ITIM-bearing receptors
					5.11.1.5.3.1. DCIR
					5.11.1.5.3.2. MICL
				5.11.1.5.4. ITAM/ITIM-independent receptors
					5.11.1.5.4.1. DC-SIGN
					5.11.1.5.4.2. MGL
					5.11.1.5.4.3. MMR
					5.11.1.5.4.4. Langerin
		5.11.2. C-type lectin receptors in immune homeostasis
			5.11.2.1. Celldeath
				5.11.2.1.1. Mincle
				5.11.2.1.2. MICL
				5.11.2.1.3. DNGR-1
				5.11.2.1.4. LOX-1
				5.11.2.1.5. Langerin
			5.11.2.2. Microbiota
				5.11.2.2.1. Dectin-1
				5.11.2.2.2. Mincle
				5.11.2.2.3. OtherCLRs
		5.11.3. C-type lectin receptors in disease processes
			5.11.3.1. Autoimmune diseases
				5.11.3.1.1. Allergic asthma
					5.11.3.1.1.1. Dectin-1
					5.11.3.1.1.2. Dectin-2
					5.11.3.1.1.3. Langerin
				5.11.3.1.2. Multiple sclerosis
					5.11.3.1.2.1. DCIR
					5.11.3.1.2.2. DC-SIGN
					5.11.3.1.2.3. Mincle/MCL
					5.11.3.1.2.4. Dectin-1
			5.11.3.2. Infectious diseases
				5.11.3.2.1. C-type lectin receptors in fungal infections
					5.11.3.2.1.1. Dectin-1
					5.11.3.2.1.2. Dectin-2
					5.11.3.2.1.3. Mincle
					5.11.3.2.1.4. DC-SIGN
					5.11.3.2.1.5. MMR
				5.11.3.2.2. C-type lectin receptors in bacterial infections
					5.11.3.2.2.1. MMR
					5.11.3.2.2.2. DC-SIGN
					5.11.3.2.2.3. Dectin-1
					5.11.3.2.2.4. Mincle
				5.11.3.2.3. C-type lectin receptors in viral infections
					5.11.3.2.3.1. DC-SIGN
					5.11.3.2.3.2. Langerin
					5.11.3.2.3.3. DCIR
					5.11.3.2.3.4. MMR
					5.11.3.2.3.5. MGL
					5.11.3.2.3.6. MDL-1
				5.11.3.2.4. C-type lectin receptors in parasitic infections
					5.11.3.2.4.1. DC-SIGN
					5.11.3.2.4.2. MMR
					5.11.3.2.4.3. Others
		5.11.4. Conclusion
		References
	5.12 Human IgG Glycosylation in Inflammation and Inflammatory Disease
		5.12.1. Preface
		5.12.2. Antibodies
			5.12.2.1. Basic structure/function
			5.12.2.2. The antibody (immunoglobulin) isotypes
			5.12.2.3. Glycosylation of normal humanIgG
		5.12.3. Impact of glycosylation on structure and function
			5.12.3.1. Stability
			5.12.3.2. IgG-Fc effector functions: Inflammatory cascades
			5.12.3.3. Catabolism, pharmacokinetics and placental transport
		5.12.4. Individual IgG-Fc glycoforms and effector activities
			5.12.4.1. Sialylation of IgG-Fc oligosaccharides
			5.12.4.2. The influence of galactosylation on IgG-Fc activities
			5.12.4.3. The influence of fucose and bisecting N-acetylglucosamine on IgG-Fc activities
		5.12.5. IgG-Fab glycosylation
		5.12.6. IgG glycosylation and disease
			5.12.6.1. Rheumatoid arthritis
			5.12.6.2. Wegener\'s granulomatosis and microscopic polyangiitis
		5.12.7. Recombinant monoclonal antibodies for therapy
		5.12.8. Conclusions and future perspectives
		References
	5.13 Glycans in Bacterial Infections: Gram-Negative Infections in the RespiratoryTract
		5.13.1. Introduction
			5.13.1.1. Bacteria and respiratory immune system
			5.13.1.2. Bacterial glycans in acute and chronic lung infections
		5.13.2. The Gram-negative ``Glycan shield´´: An overview
			5.13.2.1. Pseudomonas aeruginosa
				5.13.2.1.1. The EPS from P.aeruginosa
				5.13.2.1.2. The LPS from P.aeruginosa
			5.13.2.2. Burkholderia cepacia complex
				5.13.2.2.1. The EPS from Burkholderia cepacia complex
				5.13.2.2.2. The LPS from Burkholderia cepacia complex
			5.13.2.3. Klebsiella pneumoniae
				5.13.2.3.1. The CPS from K.pneumoniae
				5.13.2.3.2. The LPS from K.pneumoniae
			5.13.2.4. Nontypeable Haemophilus influenzae
				5.13.2.4.1. The LOS fromNTHi
			5.13.2.5. Other emerging pathogens inCF
				5.13.2.5.1. The case of Pandoraea pulmonicola
				5.13.2.5.2. The case of S.maltophilia
				5.13.2.5.3. The case of A.xylosoxidans
		5.13.3. Future perspectives
		Acknowledgment
		References
	5.14 Glycans in Chronic Obstructive Pulmonary Disease(COPD)
		5.14.1. Introduction
			5.14.1.1. Core fucose structure in N-linked glycan on transforming growth factor beta receptor II (TGF-β receptorII)
			5.14.1.2. Keratan sulfate proteoglycan and other glycosaminoglycans
			5.14.1.3. Sialyl-LewisX structure onmucin
			5.14.1.4. Lectin receptors: Siglec-9 and CLEC5A
			5.14.1.5. Glycans as biomarkers
		5.14.2. Future perspectives
		Acknowledgment
		References
	5.15 Neural Functions of Glycolipids
		5.15.1. Introduction
		5.15.2. Neural functions of galactosylceramides
			5.15.2.1. Myelin and myelination
			5.15.2.2. Dysmyelination in mice lacking galactosylceramides
			5.15.2.3. Biological roles of sulfatide
		5.15.3. Neural functions of gangliosides
			5.15.3.1. Complex ganglioside function in neuronal homeostasis and axon-myelin stabilization
			5.15.3.2. Functional roles of simple gangliosides and glycosphingolipids
			5.15.3.3. Human deficits in ganglioside biosynthesis confirm the roles of gangliosides in nervous system function and hom ...
		5.15.4. Mechanisms of glycosphingolipid action in the nervous system
			5.15.4.1. Cis regulation: GM1 enhancement of TrkA neurotrophin receptor activation drives asymmetric axonogenesis
			5.15.4.2. Trans recognition: Gangliosides as functional receptors for myelin-associated glycoprotein
			5.15.4.3. Gangliosides in lipid rafts: GD3-TAG1-Lyn signaling
		References
	5.16 Glycan-Related Demyelination and Remyelination
		5.16.1. Introduction
		5.16.2. Glycosylation-dependent astrocyte activation
		5.16.3. Brain extracellular matrix components block remyelination
		5.16.4. Loss of brain-enriched glycosylation results in impaired myelination
		5.16.5. Notch and Wnt pathways: Two critical regulators of OPC differentiation
		5.16.6. Future perspective
		References
	5.17 Role of Polysialic Acid in Schizophrenia
		5.17.1. Introduction
		5.17.2. Biochemistry of polysialicacid
		5.17.3. General symptom of schizophrenia
		5.17.4. Expression of polysialic acid in schizophrenicbrain
		5.17.5. Genetic factors of schizophrenia
		5.17.6. Biochemical analyses of the relationship between the structure and function of polysialic acid and the SNPs repor ...
		5.17.7. Mouse phenotypes and their association with schizophrenia
		5.17.8. Environmental factors and polySia expression
		5.17.9. Therapeutic effects on polySia expression
		5.17.10. Conclusion
		References
	5.18 The Involvement of Cellular Glycans in Alzheimer´s Disease
		5.18.1. Introduction
		5.18.2. Glycolipids andAD
			5.18.2.1. GM1 seed hypothesis
			5.18.2.2. Other glycolipids
		5.18.3. N-Glycan andAD
			5.18.3.1. N-Glycomicstudy
			5.18.3.2. Bisecting GlcNAc andAD
			5.18.3.3. Sialylation andAD
			5.18.3.4. Other N-glycans
		5.18.4. O-GalNAc glycan andAD
		5.18.5. O-GlcNAc andAD
		5.18.6. Other glycans andAD
			5.18.6.1. Glycosaminoglycan andAD
			5.18.6.2. Human natural killer-1 (HNK-1) epitope andAD
		5.18.7. Concluding remarks
		Acknowledgment
		References
		Relevant Websites
	5.19 Congenital Disorders of Glycosylation
		5.19.1. Introduction
		5.19.2. Basic science of glycosylation
			5.19.2.1. N-glycan synthesis
			5.19.2.2. O-glycan synthesis
			5.19.2.3. Glycosaminoglycan synthesis
			5.19.2.4. Glycosphingolipid synthesis
			5.19.2.5. GPI anchor synthesis
		5.19.3. Congenital disorders of glycosylation
			5.19.3.1. Historical perspectives
			5.19.3.2. Impaired biosynthesis of glycosylation precursors
			5.19.3.3. Defects in dolichol production
			5.19.3.4. Defects in LLO biosynthesis
			5.19.3.5. Defects in OST and TRAP complexes
			5.19.3.6. Defects in glycosidase activity
			5.19.3.7. Defects in intracellular vesicle trafficking
			5.19.3.8. Defects in Golgi homeostasis and pH maintenance
			5.19.3.9. Defects in nucleotide sugar transport
			5.19.3.10. Glycosyltransferase dysfunction in N-glycosylation
			5.19.3.11. O-glycosylation disorders
				5.19.3.11.1. Defects in O-Man glycans
				5.19.3.11.2. Defects in O-GalNAc glycans
				5.19.3.11.3. Defects in O-GlcNAc glycans
				5.19.3.11.4. Defects in O-glycosylation of collagens
				5.19.3.11.5. Defects in O-Fuc and O-Glc glycans
			5.19.3.12. Defects in glycosaminoglycan biosynthesis
			5.19.3.13. Defects in glycosphingolipid biosynthesis
			5.19.3.14. Defects in GPI anchor biosynthesis, transfer and remodeling
		5.19.4. Therapies
			5.19.4.1. Dietary supplementation
			5.19.4.2. Gene therapy
			5.19.4.3. Transplantation
			5.19.4.4. Potential therapeutic avenues in PMM2-CDG
		5.19.5. Perspectives and future directions
		Acknowledgment
		Acknowledgment
		References
	5.20 α-Dystroglycanopathy: Molecular Mechanism, Clinical Manifestations, and Therapeutic Approaches
		5.20.1. Introduction
		5.20.2. Pathophysiology and clinical manifestations of α-dystroglycanopathies
		5.20.3. Molecular mechanism
		5.20.4. Classification of α-dystroglycanopathy and clinical manifestations
		5.20.5. Treatment
			5.20.5.1. Recent advance for the treatment in neuromuscular diseases
			5.20.5.2. Antisense therapy
			5.20.5.3. Enzyme replacement therapy
			5.20.5.4. Gene therapy
			5.20.5.5. Low molecular compounds and other option
		5.20.6. Perspectives for the future of α-dystroglycanopathies
		Acknowledgment
		References
	5.21 Diseases Associated With GPI Anchors
		5.21.1. Biosynthesis of GPI-anchored proteins in mammaliancells
			5.21.1.1. Introduction
			5.21.1.2. Biosynthesis of GPI anchor precursors
				5.21.1.2.1. Step 1: PIGA, PIGC, PIGH, PIGP, PIGQ, PIGY,DPM2
				5.21.1.2.2. Step 2:PIGL
				5.21.1.2.3. Step 3: Unidentified flippase
				5.21.1.2.4. Step 4:PIGW
				5.21.1.2.5. Step 5: Lipid remodeling enzyme-not identified
				5.21.1.2.6. Step 6: PIGM,PIGX
				5.21.1.2.7. Step 7:PIGV
				5.21.1.2.8. Step 8:PIGN
				5.21.1.2.9. Step 9:PIGB
				5.21.1.2.10. Step 10: PIGO,PIGF
				5.21.1.2.11. Step 11: PIGG,PIGF
			5.21.1.3. Attachment of GPI to proteins: PIGK, PIGT, PIGS, PIGU, GPAA1
			5.21.1.4. Post GPI-attachment modifications
				5.21.1.4.1. Inositol deacylation:PGAP1
				5.21.1.4.2. Removal of the EtNP on the second mannose:PGAP5
				5.21.1.4.3. Lipid remodeling in the Golgi: PGAP3,PGAP2
				5.21.1.4.4. Side chain of the first mannose: PGAP4, B3GALT4
			5.21.1.5. FreeGPI
			5.21.1.6. Shedding GPI-APs
		5.21.2. Paroxysmal nocturnal hemoglobinuria
			5.21.2.1. Introduction
			5.21.2.2. Molecular genetics ofPNH
				5.21.2.2.1. Biochemical defects inPNH
				5.21.2.2.2. PIGAgene
				5.21.2.2.3. Somatic mutation ofPIGA
			5.21.2.3. Mechanism of clonal expansion of PNHcells
				5.21.2.3.1. A PIGA mutation is not sufficient for clonal expansion
				5.21.2.3.2. What causes clonal dominance of PNHcells?
				5.21.2.3.3. Immunological selection
					5.21.2.3.3.1. Clinical evidence
					5.21.2.3.3.2. Experimental evidence
				5.21.2.3.4. Benign tumor hypothesis
				5.21.2.3.5. Three-step model for the pathogenesis ofPNH
			5.21.2.4. Clinical aspects ofPNH
				5.21.2.4.1. Hemolytic anemia
				5.21.2.4.2. Thrombosis
				5.21.2.4.3. Bone marrow failure
			5.21.2.5. Recent topics
				5.21.2.5.1. Complement inhibitors
				5.21.2.5.2. PNH caused by the PIGT gene defects (PIGT-PNH)
		5.21.3. Inherited GPI deficiency(IGD)
			5.21.3.1. Introduction
			5.21.3.2. The first case: PIGM deficiency
			5.21.3.3. IGD caused by the decreased expression of GPI-APs
				5.21.3.3.1. IGD with hyperphosphatasia
				5.21.3.3.2. IGDs without hyperphosphatasia
			5.21.3.4. IGD caused by the structural abnormalities of GPI-APs
			5.21.3.5. Genotype-phenotype correlations inIGD
			5.21.3.6. IGD overlaps with other syndromes
			5.21.3.7. IGD overlaps with other glycosylation pathway defects
			5.21.3.8. Nomenclature ofIGD
			5.21.3.9. Future perspectives
		References
	5.22 The Enzyme-Mediated Activation of Radical Sources (EMARS) Reaction: A New Tool for Identification of Membrane Microdomain ...
		5.22.1. Introduction
		5.22.2. Development and improvement of the EMARSmethod
		5.22.3. Application of the EMARS method to cell biology
		5.22.4. Segregation of membrane microdomains using GPI-anchored HRP fusion proteins
		5.22.5. Proximity proteomics identifies the cis-bimolecular cancer target(BiCAT)
		5.22.6. Conclusion and perspective
		References
	5.23 Human Milk Oligosaccharides and Microbiome Homeostasis
		5.23.1. Introduction
		5.23.2. Human milk oligosaccharides characterization: Structural diversity ofHMOs
		5.23.3. Infant gut microbiome assembly and composition
			5.23.3.1. Deliverytype
			5.23.3.2. Length of gestation
			5.23.3.3. Antibiotics
			5.23.3.4. Breastfeeding
			5.23.3.5. HMO
		5.23.4. Infant gut microbiome and gut homeostasis
		5.23.5. Molecular mechanisms of HMOs consumption
			5.23.5.1. HMOs degraders: Bifidobacterium species
				5.23.5.1.1. Bifidobacterium longum subsp. infantis (B.infantis)
				5.23.5.1.2. Bifidobacterium bifidum
				5.23.5.1.3. Bifidobacterium breve
				5.23.5.1.4. Bifidobacterium longum subsp. longum (B.longum)
			5.23.5.2. Utilization of HMO by othertaxa
			5.23.5.3. Cross-feeding of HMOs between members of the gut microbiome
		5.23.6. Conclusions and future directions
		References
	5.24 Human Milk Oligosaccharides and Innate Immunity
		5.24.1. Introduction
		5.24.2. Chemical structures, concentration and biosynthesis ofHMOs
		5.24.3. Structural features of HMOs and recognition by endogenous lectins
			5.24.3.1. Structural units of HMOs as glycotopes
			5.24.3.2. Endogenous lectins that bind toHMOs
		5.24.4. The metabolic pathways of HMOs in bifidobacteria
			5.24.4.1. Invitro growth experiments of Bifidobacterium species in a medium containing HMOs as the sole carbon source
			5.24.4.2. The metabolism of HMOs by bifidobacteria
		5.24.5. The modulation of colonic microflora byHMOs
		5.24.6. The biological functions ofHMOs
			5.24.6.1. Antiinfection against pathogenic microorganisms
			5.24.6.2. Antiinflammation
			5.24.6.3. Prevention of necrotizing enterocolitis(NEC)
			5.24.6.4. Modification of colonic epithelium exposed to milk oligosaccharides
			5.24.6.5. Stimulation of brain activity
			5.24.6.6. Effect on malnutrition
		5.24.7. The industrial scale preparation and utilization ofHMOs
		5.24.8. Future aspects forHMOs
		5.24.9. Milk oligosaccharides in nonhuman mammals
		5.24.10. Summary
		References
	5.25 N-Linked Glycans in the Epithelial-Mesenchymal Transition: Implications for Cancer Metastasis
		References
	5.26 The Role of Glycans in Chronic Inflammatory Gastrointestinal and Liver Disorders andCancer
		5.26.1. Introduction
		5.26.2. Inflammatory hepatic disorders and livercancer
			5.26.2.1. Glycosylation profile in inflammatory liver diseases
				5.26.2.1.1. Autoimmune hepatitis
				5.26.2.1.2. Primary sclerosing cholangitis and primary biliary cholangitis
				5.26.2.1.3. Nonalcoholic fatty liver disease and nonalcoholic steatohepatitis
				5.26.2.1.4. Liver fibrosis and cirrhosis
			5.26.2.2. Altered glycans expression in Hepatocellular Carcinoma
			5.26.2.3. Glycans as biomarkers for clinical diagnosis and prognosis of inflammatory hepatic disorders and hepatocellular ...
		5.26.3. Chronic inflammatory intestinal disorders
			5.26.3.1. Intestinal glycocalyx and its regulatory functions in Inflammatory Bowel Disease
			5.26.3.2. T-cell glycosylation: From cell biology to inflammatory bowel disease therapy
			5.26.3.3. Glycans: New tools for the diagnostic and prognostic algorithm of Inflammatory Bowel Disease
		5.26.4. Stomach and colorectalcancer
			5.26.4.1. Changes in Glycans signature associated with Gastric and Colorectal Cancers development and progression
			5.26.4.2. Remodeling of Glycome as a promising strategy for Gastric and Colorectal Cancers treatment and prevention
			5.26.4.3. Altered glycans expression in Gastric and Colorectal cancers: Impact in cancer immunoediting and immunesurveillance
		5.26.5. Summary
		References
	5.27 Glycan Biomarkers in PancreaticCancer
		5.27.1. Introduction
			5.27.1.1. Identification of Fuc-Hpt as AAL-binding protein in sera of patients with pancreatic cancer and development of  ...
			5.27.1.2. Site-directed glyco-peptide analysis of haptoglobin
			5.27.1.3. Establishment of novel glycan antibody for Fuc-Hpt
			5.27.1.4. Serum Fuc-Hpt levels determined with 10-7G mAb ELISA were increased in patients with pancreatic cancer and colo ...
			5.27.1.5. Serum Hpt and Fuc-Hpt levels in healthy volunteers and pancreatic cancer patients according to each Hpt phenotype
			5.27.1.6. Determination of the epitope of 10-7GmAb
			5.27.1.7. Hepatocytes surrounding metastasized pancreatic cancer cells produce the 10-7G mAb-reactingHpt
		5.27.2. Conclusions
		Acknowledgment
		Acknowledgment
		Acknowledgment
		References
	5.28 Xenotransplantation and Glycomedicine
		Glossary
		Nomenclature
		5.28.1. Introduction
		5.28.2. The α-Gal epitope
			5.28.2.1. History
			5.28.2.2. Approach based on xenograft research
			5.28.2.3. The α1,3GTgene
		5.28.3. Remodeling of the major xeno-glycoantigen
			5.28.3.1. α-Galactosidase treatment
			5.28.3.2. Endo-β-galactosidase C(EndoGalC) treatment
			5.28.3.3. Substrate competition in core glycosylation: GnT-III
			5.28.3.4. Substrate competition in terminal glycosylation 1: Fucosyltransferase(FT)
			5.28.3.5. Substrate competition in terminal glycosylation 2: Sialyltransferase(ST)
			5.28.3.6. GP3ST
		5.28.4. Transgenic pigs with glycosyltransferase
			5.28.4.1. The α1,2FTpig
			5.28.4.2. The α2,3STpig
			5.28.4.3. The GnT-IIIpig
			5.28.4.4. The EndoGalCpig
		5.28.5. Knock out(KO)
			5.28.5.1. Previous prospect
			5.28.5.2. Pig α1,3GTgene
			5.28.5.3. Knockout
				5.28.5.3.1. The production of anti-Gal antibodies in GalT-KOPigs
			5.28.5.4. Neoantigen in the GalT KOpigs
			5.28.5.5. The quantitative analysis of non-Gal antigens
		5.28.6. iGb3 synthase
		5.28.7. The non-Gal antigen
			5.28.7.1. The H-D antigen
			5.28.7.2. The H-D antibody
			5.28.7.3. Regulation of the H-D antigen
			5.28.7.4. Pig CMAHgene
			5.28.7.5. The CMAH-KOPig
		5.28.8. The non-Gal antigen: Sda/CAD antigen
		5.28.9. Other unknown glycoantigens
		5.28.10. Expression of glycoantigens in islets
		5.28.11. Innate immunological cells and glycoantigen
			5.28.11.1. Natural killer (NK) cell receptor
			5.28.11.2. Macrophages and Siglecs
			5.28.11.3. The suppression of macrophage by SP-D
		5.28.12. Platelet sequestration in liver xenotransplantation
		5.28.13. PERV infectivity to human cell and N-linked sugars
		References
	5.29 Glycans as Targets and Mediators of T-Cell Immunotherapy
		Glossary
		5.29.1. An introduction to T-cell immunotherapy
			5.29.1.1. Adoptive T-cell immunotherapies
		5.29.2. Glycans as targets of CAR T-cells
		5.29.3. The role of glycans in T-cell biology
			5.29.3.1. Glycans throughout T-cell development
			5.29.3.2. T-cell avidity
			5.29.3.3. Glycans regulate susceptibility to celldeath
		5.29.4. The role of glycans in Tcell trafficking and its implications for immunotherapy
			5.29.4.1. Glycans in steady state T-cell homing and during inflammation
			5.29.4.2. Glycans in T-cell trafficking into malignant tissues and immune evasion
			5.29.4.3. Improving T-cell migration into tumors
				5.29.4.3.1. Glycoengineering to enhance T-cell homing
				5.29.4.3.2. Targeting the tumor microenvironment
		5.29.5. A look toward the future
		Acknowledgment
		References
	5.30 Glycotherapeutics and Verotoxin
		5.30.1. Introduction
		5.30.2. Verotoxin-induced pathology
			5.30.2.1. Hemolytic uremic syndrome
			5.30.2.2. Verotoxin GSL receptor binding
			5.30.2.3. Verotoxin Gb3-bindingsite
				5.30.2.3.1. B subunit co-crystal versus modeling structure
			5.30.2.4. Gb3 tissue distribution and verotoxin pathology
				5.30.2.4.1. Gb3 lipidrafts
				5.30.2.4.2. Cholesterol maskingGSLs
			5.30.2.5. Gb3 receptor mimics as an approach to the prevention of VT1-induced pathology
				5.30.2.5.1. Probiotic approach
				5.30.2.5.2. Chemical approaches
					5.30.2.5.2.1. Insoluble matrices
					5.30.2.5.2.2. Soluble Gb3 mimics
						5.30.2.5.2.2.1. Starfish
						5.30.2.5.2.2.2. Supertwig
						5.30.2.5.2.2.3. Soluble monomeric Gb3 glycolipid mimics
						5.30.2.5.2.2.4. AminoGb4
		5.30.3. Gb3 mimics inhibit HIV infection
		5.30.4. Verotoxin as an antineoplastic
			5.30.4.1. MDR1 plays a role in Gb3 synthesis
			5.30.4.2. VT1 antineoplastic activity invivo
		5.30.5. Conclusions
		References
	5.31 Structural and Functional Roles of the N-Glycans in Therapeutic Antibodies
		Glossary
		5.31.1. Introduction
		5.31.2. Structural heterogeneity ofIgG
		5.31.3. Functional impacts of IgG N-glycosylation
		5.31.4. Structural delineation of IgG-Fc as glycoprotein
		5.31.5. Structural basis of Fc-FcγR interactions
		5.31.6. Dynamic views of glycosylation-dependent IgG functions
		5.31.7. Concluding remarks and perspective
		Acknowledgment
		References
	Index
	Back Cover