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More About This Title Analyzing Biomolecular Interactions by MassSpectrometry
English
Arranged in three parts, the text begins by reviewing techniques nowadays almost considered classical, such as affinity chromatography and ultrafiltration, as well as the latest techniques. The second part focusses on all MS-based methods for the study of interactions of proteins with all classes of biomolecules. Besides pull down-based approaches, this section also emphasizes the use of ion mobility MS, capture-compound approaches, chemical proteomics and interactomics. The third and final part discusses other important technologies frequently employed in interaction studies, such as biosensors and microarrays.
For pharmaceutical, analytical, protein, environmental and biochemists, as well as those working in pharmaceutical and analytical laboratories.
English
Wilfried M.A. Niessen studied chemistry at the VU University Amsterdam. After his PhD, he worked for 9 years as an analytical chemist within the Leiden/ Amsterdam Center for Drug Research at Leiden University. After leaving the university in 1996, he started the company hyphen MassSpec, providing independent consultancy and training in the field of analytical mass spectrometry. In parallel to this, he was extraordinary professor in bioanalytical mass spectrometry at the Faculty of Science of the VU University Amsterdam between 2002 and 2014. There, he was involved in high-resolution screening and the role of MS therein. His main research interests involve principles, instrumentation and applications of liquid chromatography-mass spectrometry as well as interpretation of small-molecule MS-MS mass spectra. He is (co)author of more than 200 peer reviewed publications in the field of LC-MS and more than 40 book chapters. Wilfried Niessen authored and edited five books, and was guest editor on several special journal issues.
English
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 Lemière, 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 Höfner 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. Calderón
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, José María Gutiérrez, 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
