Analyzing Biomolecular Interactions by Mass Spectrometry

Content: List of Contributors XIII     Preface XVII     Abbreviations XIX     1 Introduction to Mass Spectrometry, a Tutorial 1 Wilfried M.A. Niessen and David Falck     1.1 Introduction 1     1.2 Figures of Merit 1     1.2.1 Introduction 1     1.2.2 Resolution 2     1.2.3 Mass Accuracy 4     1.2.4 General Data Acquisition in MS 5     1.3 Analyte Ionization 6     1.3.1 Introduction 6     1.3.2 Electrospray Ionization 8     1.3.3 Matrix-Assisted Laser Desorption Ionization 10     1.3.4 Other Ionization Methods 10     1.3.5 Solvent and Sample Compatibility Issues 11     1.4 Mass Analyzer Building Blocks 12     1.4.1 Introduction 12     1.4.2 Quadrupole Mass Analyzer 13     1.4.3 Ion-Trap Mass Analyzer 13     1.4.4 Time-of-Flight Mass Analyzer 15     1.4.5 Fourier Transform Ion Cyclotron Resonance Mass Spectrometer 16     1.4.6 Orbitrap Mass Analyzer 17     1.4.7 Ion Detection 18     1.5 Tandem Mass Spectrometry 18     1.5.1 Introduction:    Tandem-in-Time    and    Tandem-in-Space    18     1.5.2 Ion Dissociation Techniques 20     1.5.3 Tandem Quadrupole MS   MS Instruments 21     1.5.4 Ion-Trap MSn Instruments 23     1.5.5 Tandem TOF (TOF   TOF) Instruments 23     1.5.6 Hybrid Instruments (Q   TOF, Q   LIT, IT   TOF) 24     1.5.7 MS   MS and MSn in FT-ICR-MS 26     1.5.8 Orbitrap-Based Hybrid Systems 27     1.5.9 Ion-Mobility Spectrometry   Mass Spectrometry 28     1.6 Data Interpretation and Analytical Strategies 30     1.6.1 Data Acquisition in MS Revisited 30     1.6.2 Quantitative Bioanalysis and Residue Analysis 31     1.6.3 Identification of Small-Molecule    Known Unknowns    32     1.6.4 Identification of Drug Metabolites 33     1.6.5 Protein Molecular Weight Determination 37     1.6.6 Peptide Fragmentation and Sequencing 38     1.6.7 General Proteomics Strategies: Top-Down, Middle-Down, Bottom-Up 39     1.7 Conclusion and Perspectives 43     References 43     Part I Direct MS Based Affinity Techniques 55     2 Studying Protein   Protein Interactions by Combining Native Mass Spectrometry and Chemical Cross-Linking 57 Michal Sharon and Andrea Sinz     2.1 Introduction 57     2.2 Protein Analysis by Mass Spectrometry 58     2.3 Native MS 59     2.3.1 Instrumentation for High-mass ion Detection 60     2.3.2 Defining the Exact Mass of the Composing Subunits 60     2.3.3 Analyzing the Intact Complex 61     2.4 Chemical Cross-linking MS 64     2.4.1 Types of Cross-linkers 64     2.4.2 MS/MS Cleavable Cross-linkers 66     2.4.3 Data Analysis 68     2.5 Value of Combining NativeMS with Chemical Cross-linkingMS 68     2.6 Regulating the Giant 69     2.7 Capturing Transient Interactions 70     2.8 An Integrative Approach for Obtaining Low-Resolution Structures of Native Protein Complexes 72     2.9 Future Directions 73     References 74     3 Native Mass Spectrometry Approaches Using Ion Mobility-Mass Spectrometry 81 Frederik Lermyte, Esther Marie Martin, Albert Konijnenberg, Filip Lemiere, and Frank Sobott     3.1 Introduction 81     3.2 Sample Preparation 82     3.3 Electrospray Ionization 84     3.4 Mass Analyzers and Tandem MS Approaches 88     3.5 Ion Mobility 90     3.6 Data Processing 95     3.7 Challenges and Future Perspectives 98     References 102     Part II LC   MS Based with Indirect Assays 109     4 Methodologies for Effect-Directed Analysis: Environmental Applications, Food Analysis, and Drug Discovery 111 Willem Jonker, Marja Lamoree, Corine J. Houtman, and Jeroen Kool     4.1 Introduction 111     4.2 Principle of Traditional Effect-Directed Analysis 113     4.3 Sample Preparation 113     4.3.1 Environmental Analysis 113     4.3.2 Food Analysis 121     4.3.3 Drug Discovery 124     4.4 Fractionation for Bioassay Testing 126     4.4.1 Environmental Analysis 126     4.4.2 Food Analysis 130     4.4.3 Drug Discovery 131     4.5 Miscellaneous Approaches 133     4.6 Bioassay Testing 136     4.6.1 Environmental Analysis 136     4.6.2 Food Analysis 140     4.6.3 Drug Discovery 140     4.7 Identification and Confirmation Process 141     4.7.1 Instrumentation 141     4.7.2 Data Analysis 143     4.8 Conclusion and Perspectives 148     References 149     5 MS Binding Assays 165 Georg Hofner and Klaus T.Wanner     5.1 Introduction 165     5.2 MS Binding Assays     Strategy 167     5.2.1 Analogies and Differences Compared to Radioligand Binding Assays 167     5.2.2 Fundamental Assay Considerations 169     5.2.3 Fundamental Analytical Considerations 170     5.3 Application of MS Binding Assays 171     5.3.1 MS Binding Assays for the GABA Transporter GAT1 171     5.3.2 MS Binding Assays for the Serotonin Transporter 183     5.3.3 MS Binding Assays Based on the Quantitation of the Nonbound Marker 187     5.3.4 Other Examples Following the Concept of MS Binding Assays 189     5.4 Summary and Perspectives 191     Acknowledgments 192     References 192     6 Metabolic Profiling Approaches for the Identification of Bioactive Metabolites in Plants 199 Emily Pipan and Angela I. Calderon     6.1 Introduction to Plant Metabolic Profiling 199     6.2 Sample Collection and Processing 200     6.3 Hyphenated Techniques 203     6.3.1 Liquid Chromatography   Mass Spectrometry 203     6.3.2 Gas Chromatography   Mass Spectrometry 206     6.3.3 Capillary Electrophoresis   Mass Spectrometry 207     6.4 Mass Spectrometry 207     6.4.1 Time of Flight 208     6.4.2 Quadrupole Mass Filter 208     6.4.3 Ion Traps (Orbitrap and Linear Quadrupole (LTQ)) 209     6.4.4 Fourier Transform Mass Spectrometry 210     6.4.5 Ion Mobility Mass Spectrometry 210     6.5 Mass Spectrometric Imaging 210     6.5.1 MALDI-MS 211     6.5.2 SIMS-MS 212     6.5.3 DESI-MS 212     6.5.4 LAESI-MS 213     6.5.5 LDI-MS and Others for Imaging 213     6.6 Data Analysis 214     6.6.1 Data Processing 214     6.6.2 Data Analysis Methods 214     6.6.3 Databases 215     6.7 Future Perspectives 216     References 216     7 Antivenomics: A Proteomics Tool for Studying the Immunoreactivity of Antivenoms 227 Juan J. Calvete, Jose Maria Gutierrez, Libia Sanz, Davinia Pla, and Bruno Lomonte     7.1 Introduction 227     7.2 Challenge of Fighting Human Envenoming by Snakebites 227     7.3 Toolbox for Studying the Immunological Profile of Antivenoms 228     7.4 First-Generation Antivenomics 229     7.5 Snake Venomics 230     7.6 Second-Generation Antivenomics 232     7.7 Concluding Remarks 236     Acknowledgments 236     References 236     Part III Direct Pre- and On-Column Coupled Techniques 241     8 Frontal and Zonal Affinity Chromatography Coupled to Mass Spectrometry 243 Nagendra S. Singh, Zhenjing Jiang, and Ruin Moaddel     8.1 Introduction 243     8.2 Frontal Affinity Chromatography 244     8.3 Staircase Method 247     8.4 Simultaneous Frontal Analysis of a Complex Mixture 249     8.5 Multiprotein Stationary Phase 252     8.6 Zonal Chromatography 253     8.7 Nonlinear Chromatography 260     Acknowledgments 265     References 265     9 Online Affinity Assessment and Immunoaffinity Sample Pretreatment in Capillary Electrophoresis   Mass Spectrometry 271 Rob Haselberg and Govert W. Somsen     9.1 Introduction 271     9.2 Capillary Electrophoresis 272     9.3 Affinity Capillary Electrophoresis 276     9.3.1 Dynamic Equilibrium ACE (Fast Complexation Kinetics) 276     9.3.2 Pre-Equilibrium ACE (Slow Complexation Kinetics) 279     9.3.3 Kinetic ACE (Intermediate Complexation Kinetics) 280     9.4 Immunoaffinity Capillary Electrophoresis 281     9.5 Capillary Electrophoresis   Mass Spectrometry 283     9.5.1 General Requirements for Effective CE   MS Coupling 283     9.5.2 Specific Requirements for ACE   MS and IA-CE-MS 284     9.6 Application of ACE   MS 286     9.7 Applications of IA-CE   MS 292     9.8 Conclusions 295     References 296     10 Label-Free Biosensor Affinity Analysis Coupled to Mass Spectrometry 299 David Bonnel, Dora Mehn, and Gerardo R. Marchesini     10.1 Introduction to MS-Coupled Biosensor Platforms 299     10.2 Strategies for Coupling Label-Free Analysis with Mass Spectrometry 301     10.2.1 On-Chip Approaches 301     10.2.2 Off-Chip Configurations 305     10.2.3 Chip Capture and Release Chromatography     Electrospray-MS 306     10.3 New Sensor and MS Platforms, Opportunities for Integration 307     10.3.1 Imaging Nanoplasmonics 307     10.3.2 EvanescentWave SiliconWaveguides 308     10.3.3 New Trends in MS Matrix-Free Ion Sources 309     10.3.4 Tag-Mass 310     10.3.5 Integration 310     References 310     Part IV Direct Post Column Coupled Affinity Techniques 317     11 High-Resolution Screening: Post-Column Continuous-Flow Bioassays 319 David Falck,Wilfried M.A. Niessen, and Jeroen Kool     11.1 Introduction 319     11.1.1 Variants of On-line Post-Column Assays Using Mass Spectrometry 321     11.1.2 Targets and Analytes 328     11.2 The High-Resolution Screening Platform 330     11.2.1 Separation 330     11.2.2 Flow Splitting 334     11.2.3 Bioassay 336     11.2.4 MS Detection 340     11.3 Data Analysis 342     11.3.1 Differences between HRS and HTS 342     11.3.2 Validation 350     11.4 Conclusions and Perspectives 353     11.4.1 The Relation of On-line Post-Column Assays to Other Formats 353     11.4.2 Trends in High-Resolution Screening 354     11.4.3 Conclusions 357     References 358     12 Conclusions 365 Jeroen Kool     Index 373