Antimicrobial peptides : discovery, design and novel therapeutic strategies

Contents......Page 5
Contributors......Page 11
Preface......Page 13
Introduction......Page 15
1 A Database View of Naturally Occurring Antimicrobial Peptides: Nomenclature, Classification and Amino Acid Sequence Analysis......Page 19
1.1 Database Scope and Overview......Page 20
1.2 Nomenclature of Antimicrobial Peptides......Page 21
1.3 Annotation and Classification of Antimicrobial Peptides......Page 23
1.4 Amino Acid Sequence Analysis of Antimicrobial Peptides......Page 33
1.5 Concluding Remarks......Page 35
2.1 Introduction to Bacteriocins......Page 40
2.2 Biosynthesis and Post-translational Modifications......Page 41
2.3 Classification......Page 42
2.4 Lantibiotic Subgroups: Biology, Structure and Mode of Action......Page 43
2.5 Current and Future Use of Lantibiotics for Food Applications......Page 47
2.7 Engineering of Lantibiotics......Page 48
2.8 Screening for New Lantibiotics......Page 49
2.9 Concluding Remarks and Perspectives......Page 50
3.1 Introduction to Plant Antimicrobial Peptides......Page 58
3.2 Cyclotides......Page 67
3.3 Concluding Remarks and Perspectives......Page 81
4 Database-aided Prediction and Design of Novel Antimicrobial Peptides......Page 90
4.1 Database-aided Antimicrobial Peptide Prediction......Page 91
4.2 Database-aided Peptide Design and Improvement......Page 94
4.3 Strategies for Improving Cell Selectivity of AMPs......Page 98
4.5 Concluding Remarks......Page 100
5.1 The Interfacial Activity Model of AMP Activity......Page 105
5.2 Combinatorial Chemistry Methods......Page 106
5.3 High-throughput Screening......Page 108
5.4 Accomplishments......Page 115
5.5 Future Directions......Page 116
6.1 Introduction......Page 118
6.2 De Novo-designed Rigid Peptidomimetics......Page 120
6.3 Acyl-lysyl Oligomers......Page 122
6.4 Concluding Remarks and Perspectives......Page 128
7.1 Differences in Chemical Composition and Molecular Organization of Gram-positive and Gram-negative Bacteria......Page 134
7.2 Role of Bacterial Membrane Lipid Composition in Antimicrobial Sensitivity......Page 136
7.3 Antimicrobial Agents that Target the Outer Membrane of Gram-negative Bacteria......Page 137
7.4 Antimicrobial Agents that Promote Clustering of Anionic Lipids......Page 138
7.5 Concluding Remarks and Perspectives......Page 143
8.1 Introduction......Page 146
8.2 Buforin II: α-Helical AMP with Single Proline Residue Binding to Nucleic Acids......Page 148
8.3 PR-39 and Indolicidin: Mammalian Proline-rich Peptides Inhibiting Macromolecule Synthesis and Cell Division......Page 149
8.4 Apidaecin, Drosocin and Pyrrhocoricin: Short, Insect Proline-rich Peptides Binding to Heat-shock Protein DnaK......Page 151
8.5 Concluding Remarks and Perspectives......Page 154
9.1 Human Defensins and Cathelicidins......Page 159
9.2 Bacterial Expression and Purification of Antimicrobial Peptides......Page 161
9.3 Structural Studies of Membrane-targeting Antimicrobial Peptides......Page 164
9.4 Structure-based Peptide Engineering......Page 177
9.5 Concluding Remarks and Perspectives......Page 178
10.1 Introduction......Page 187
10.2 Production of Anionic Polyelectrolytes by Host and Microbial Sources......Page 189
10.4 Releasing LL-37 from Polyelectrolyte Bundles......Page 190
10.5 Designing Antimicrobial Agents Resistant to Inactivation by Polyelectrolytes......Page 192
10.6 Possible Therapeutic Use......Page 193
10.7 Conclusion......Page 194
11.2 Early History of Vitamin D......Page 199
11.4 Vitamin D Signalling and Mechanisms of Action......Page 200
11.5 Overview of Vitamin D and Immune System Regulation......Page 202
11.7 Antimicrobial Peptides......Page 203
11.8 Regulation of DEFB2/hBD-2 Expression by 1,25D......Page 204
11.9 1,25D Regulation of LL-37 is Human and Primate Specific......Page 205
11.10 Broader Physiological and Pathophysiological Implications of the Regulation of LL-37 Expression by 1,25D......Page 206
11.11 Therapeutic Role for Vitamin D Analogues......Page 208
12 Fine Tuning Host Responses in the Face of Infection: Emerging Roles and Clinical Applications of Host Defence Peptides......Page 213
12.1 Mammalian Host Defence (Antimicrobial) Peptides......Page 214
12.2 The Role of Endogenous Host Defence Peptides in the Response to Infection......Page 216
12.3 Potential Therapeutic Uses beyond Anti-infective Activity......Page 220
12.4 Recent Clinical Advances in Therapeutic Application of Host Defence Peptides......Page 224
12.5 Innate Defence Regulators as Anti-infective Therapeutics......Page 226
12.7 Limitations and Challenges......Page 227
12.8 Conclusions......Page 229
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I......Page 243
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Z......Page 248