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Mass Spectrometry-Based Chemical Proteomics




Mass Spectrometry-Based Chemical Proteomics

W. Andy Tao (Editor), Ying Zhang (Editor)

ISBN: 978-1-118-96955-7 September 2019 432 Pages


Emphasizing mass spectrometry, this book provides strategies and concepts for understanding and analyzing chemical proteomics, their functions, modifications, and interactions. Chapters cover technical advances and applications in drug discovery, from target identification to validation and potential treatments.

  • Provides a basic overview of chemical proteomics, up-to-date concepts, analysis, and target validation
  • Covers fundamentals and strategies, including proteome profiling and chemical probes
  • Explains technical advances in the field and describes on shotgun proteomics, protein profiling, quantitative proteomics, peptide biosensors, and glycoprotein analysis
  • Includes a wide variety of applications in drug discovery, from drug targets to the chemoproteomics analysis of natural products


Chapter 1: Protein Analysis by Shotgun Proteomics

1.1 Introduction

1.2 Overview of shotgun proteomics

1.3 Sample preparation

1.4 Peptide separation and data acquisition

1.5 Informatics

Chapter 2: Quantitative Proteomics for Analyses of Multiple Samples in Parallel with Chemical Perturbation

2.1  Introduction

2.2  Relative and absolute label-free quantitation strategies

2.3  Stable isotope-based quantitative proteomics

2.4  Conclusion

2.5  Methodology

Chapter 3: Chemoproteomic Analyses by Activity-based Protein Profiling

3.1 Introduction

3.2 How ABPP works

3.3 ABPP probe design

3.4 ABPP and mass spectrometry for chemoproteomics

3.5 ABPP applications and recent advances

3.6 Conclusions and the outlook of ABPP

Chapter 4: Activity-based Probes for Profiling Protein Activities

4.1 Introduction

4.2 Analytical platforms for ABPP

4.3 Classes of enzymes studied by ABPP

4.4 Conclusions

Chapter 5: Chemical Probes for Proteins and Networks

5.1 Introduction

5.2 Application of metabolic chemical probes to lipidated protein networks

5.3 Chemical probes for target identification

5.4 Protocol

Chapter 6: Probing Kinase Activities with Peptide and Peptidomimetic Biosensors

6.1 Introduction

6.2 Peptide biosensors for assignment and characterization of enzymatic reactions and substrate specificity

6.3 Screening inhibitors and detecting ligand interactions

6.4 Diagnostic and clinical applications

6.5 Profiling enzymatic activity

6.6 Protocol

6.7 Conclusion

Chapter 7: Chemoselective Tagging to Promote Natural Product Discovery

7.1 Introduction

7.2 Non-reversible mass spectrometry tags

7.3 Reversible enrichment tags

7.4 Conclusions

7.5 Protocol for enrichment of carboxylic acid-containing natural products

Chapter 8: Identification and Quantification of Newly Synthesized Proteins Using Mass Spectrometry-based Chemical Proteomics

8.1 Introduction

8.2 Protein labeling to study newly synthesized proteins

8.3 Global identification of newly synthesized proteins by non-canonical amino acids and MS

8.4 Comprehensive quantification of newly synthesized proteins by MS

8.5 Materials

8.6 Methods

Chapter 9: Tracing Endocytosis by Mass Spectrometry

9.1 Introduction

9.2 Clathrin-mediated endocytosis

9.3 Mass spectrometry as a tool to study endocytosis

9.4 Protocols for TITAN

Chapter 10: Functional Identification of Target by Expression Proteomics (FITExP)

10.1 Introduction

10.2 FITExP Protocol

Chapter 11: Target discovery using Thermal Proteome Profiling

11.1 Introduction

11.2 Thermodynamics of ligand binding as a measure of target engagement

11.3 Thermal proteome profiling – Proteome-wide detection of drug-target interactions

11.4 Experimental formats

11.5 Experimental protocol

11.6 Present challenges with TPP

11.7 CETSA to TPP – where are we heading?

Chapter 12: Chemical Strategies to Glycoprotein Analysis

12.1 Introduction

12.2 Sample preparation strategies for glycoproteomics

12.3 MS Analysis

12.4 Conclusions

Chapter 13: Proteomic Analysis of Protein-lipid Modifications: Significance and Application

13.1 Introduction

13.2 Chemical proteomic approach to identify lipidated proteins

13.3 Protocol for Proteomic Analysis of Prenylated Proteins

Chapter 14: Site-Specific Characterization of Asp- and Glu- ADP-ribosylation by Quantitative Mass Spectrometry

14.1 Introduction

14.2 Materials

14.3 Methods

14.4 Notes

Chapter 15: MS-based Hydroxyl Radical Footprinting: Methodology and Application of Fast Photochemical Oxidation of Proteins (FPOP)

15.1 Introduction

15.2 Generation of Hydroxyl Radicals

15.3 Fast photochemical oxidation of proteins (FPOP)

15.4 Applications of FPOP

15.5 Conclusions