Modern Methods of Drug Design and Development
- 1st Edition, Volume 690 - October 17, 2023
- Imprint: Academic Press
- Editor: Matthew Lloyd
- Language: English
- Hardback ISBN:9 7 8 - 0 - 4 4 3 - 1 5 8 7 1 - 1
- eBook ISBN:9 7 8 - 0 - 4 4 3 - 1 5 8 7 2 - 8
Modern Methods of Drug Design and Development, a volume in the Methods in Enzymology series highlights new advances in the field with this new volume presenting interesting chap… Read more
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Request a sales quoteModern Methods of Drug Design and Development, a volume in the Methods in Enzymology series highlights new advances in the field with this new volume presenting interesting chapters on a variety of topics, including Recombinant protein purification for structural and kinetic studies, Steady-state kinetic analysis of reversible enzyme inhibitors, Steady-State Enzyme Kinetics, Analysis of enzyme kinetic data using ICEKAT, NMR techniques in drug discovery, Dynamic simulations and pre-steady state kinetics to guide drug discovery, Design and assay of substrate-product analogues for racemases and epimerases, Sensitive high throughput methods to screen for P450 inhibition: A- MI complex forming drugs, and more.
Other chapters cover Sensitive high throughput methods to screen for P450 inhibition: B-Heme loss causing drugs, Discovery and development of inhibitors of acetyltransferase Eis to combat Mycobacterium tuberculosis, Crystallographic fragment screening in academic cancer drug discovery, Fast fragment- and compound-screening pipeline at the Swiss Light Source, Chemical biology, enzymology and drug discovery, PROTACs, Proximity-Induced Pharmacology (PROTACs), and much more.
- Provides the authority and expertise of leading contributors from an international board of authors
- Presents the latest release in the Methods in Enzymology series
- Updated release includes the latest information on Modern Methods of Drug Design and Development
Biochemists, biophysicists, molecular biologists, analytical chemists, and physiologists
- Cover image
- Title page
- Table of Contents
- Series Page
- Copyright
- Contributors
- Preface
- References
- Chapter One: Recombinant protein production for structural and kinetic studies: A case study using M. tuberculosis α-methylacyl-CoA racemase (MCR)
- Abstract
- Abbreviations
- 1 Introduction
- 2 Recombinant protein production
- 3 Recombinant protein purification
- 4 Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE)
- Acknowledgements
- References
- Chapter Two: Steady-state kinetic analysis of reversible enzyme inhibitors: A case study on calf intestine alkaline phosphatase
- Abstract
- Abbreviations
- 1 Introduction
- 2 Measurements of 4-nitrophenol pKa
- 3 Alkaline phosphatase assays
- Acknowledgments
- References
- Chapter Three: Non-equilibrium modalities of inhibition: Characterizing irreversible inhibition for the ErbB receptor family members
- Abstract
- Abbreviations
- 1 Introduction
- 2 Protocol
- References
- Chapter Four: Analysis of continuous enzyme kinetic data using ICEKAT
- Abstract
- Abbreviations
- 1 Introduction
- 2 Program implementation
- 3 User’s guide to ICEKAT
- 4 Data processing
- 5 Expected outcomes, advantages, and limitations
- 6 Conclusions
- Acknowledgments
- References
- Chapter Five: You get what you screen for: Standards for experimental design and data fitting in drug discovery
- Abstract
- Abbreviations
- 1 An introduction to mechanism-based computer simulation and data fitting
- 3 Modeling and fitting equilibrium binding data
- 4 Signals for measuring equilibrium binding and kinetics
- 5 Global data fitting
- 6 Summary
- References
- Chapter Six: Analysis of enzyme reactions using NMR techniques: A case study with α-methylacyl-CoA racemase (AMACR)
- Abstract
- Abbreviations
- 1 Introduction
- 2 Purification of recombinant human AMACR 1A
- 3 Synthesis and quantification of acyl-CoA substrates
- 4 NMR assays of recombinant human AMACR 1A
- Acknowledgments
- References
- Chapter Seven: Crystallographic fragment screening in academic cancer drug discovery
- Abstract
- Abbreviations
- 1 Introduction
- 2 Experimental workflow and key considerations
- 3 Soaking fragments
- 4 Harvesting crystals for data collection
- 5 Data collection
- 6 Structure solution and refinement
- 7 Expected outcomes
- 8 Optimisation and troubleshooting
- 9 Summary
- 10 General safety statement
- Acknowledgements
- References
- Chapter Eight: Fast fragment and compound screening pipeline at the Swiss Light Source
- Abstract
- Abbreviations
- 1 Introduction
- 2 Before you begin
- 3 Key resources table
- 4 Materials and equipment
- 5 Step-by-step method details
- 6 Safety considerations and standards
- 7 Crystal growth and handling for crystallography-based fragment screening at the Swiss Light Source
- 8 Software for fast fragment and compound screening pipeline at the Swiss Light Source
- 9 Beamlines and data collection for crystallography-based fragment screening at the Swiss Light Source
- 10 Data evaluation and hit identification
- 11 Expected outcomes
- 12 Advantages and limitations
- 13 Alternative crystallography-based fragment screening pipelines
- 14 Concluding remarks
- Acknowledgments
- References
- Chapter Nine: Fragment-based screening by protein-detected NMR spectroscopy
- Abstract
- Abbreviations
- 1 Introduction
- 2 Target selection and preparation
- 3 Fragment library assembly and maintenance
- 4 Primary screen
- 5 Hit validation and optimization
- 6 Expected Outcomes
- 7 Advantages
- 8 Optimization and troubleshooting
- 9 Conclusion
- 10 Safety considerations
- Acknowledgments
- References
- Chapter Ten: Methods for computer-assisted PROTAC design
- Abstract
- Abbreviations
- 1 Introduction
- 2 PROTAC modeling methods
- 3 General preparation for PROTAC screening
- 4 Key resources table
- 5 Materials and equipment
- 6 Step-by-step method details
- 7 Expected outcomes
- 8 Quantification and statistical analysis
- 9 Advantages
- 10 Limitations
- 11 Optimization and troubleshooting
- 12 Summary
- Acknowledgments
- References
- Chapter Eleven: High-throughput cytochrome P450 loss and metabolic intermediate complex assays to aid in designing out of CYP3A inactivation
- Abstract
- Abbreviations
- 1 Introduction
- 2 Equipment
- 3 Reagents
- 4 Plate-based reduced carbon monoxide binding assay
- 5 P450 loss assay
- 6 Metabolic intermediate complex assay
- 7 Data processing and statistics
- 8 Method optimization and troubleshooting
- 9 Expected outcomes, advantages and limitations
- 10 Safety considerations and standards
- Acknowledgments
- References
- Chapter Twelve: Discovery and development of inhibitors of acetyltransferase Eis to combat Mycobacterium tuberculosis
- Abstract
- Abbreviations
- 1 Introduction
- 2 Method: Discovery and characterization of Eis inhibitors
- 3 Application of the method to other acetyltransferases
- References
- Chapter Thirteen: Design and evaluation of substrate–product analog inhibitors for racemases and epimerases utilizing a 1,1-proton transfer mechanism
- Abstract
- Abbreviations
- 1 Introduction
- 2 Substrate–product analogs: Design strategy
- 3 Substrate–product analogs with polar moieties
- 4 Substrate–product analogs with nonpolar moieties
- 5 Advantages and limitations of the SPA design strategy
- 6 Systematic design of substrate–product analogs
- 7 Concluding remarks
- Acknowledgments
- References
- Chapter Fourteen: Identification and biochemical characterization of small molecule inhibitors of ERK2 that target the D-recruitment site
- Abstract
- Abbreviations
- 1 Introduction
- 2 Key resources
- 3 Identifying small molecules that bind to the ERK2 DRS by fluorescence anisotropy assay
- 4 Evaluating hit small molecules for inhibition of ERK2 functions
- 5 Summary
- Acknowledgments
- References
- Chapter Fifteen: Preparing recombinant “Split AEP” for protein labeling
- Abstract
- Abbreviations
- 1 Introduction
- 2 Key resource table
- 3 Materials and equipment
- 4 Procedure
- 5 Expected outcomes
- 6 Quantification and statistical analysis
- 7 Advantages
- 8 Limitations
- 9 Optimization and troubleshooting
- 10 Alternative methods/procedures
- 11 Safety concern
- 12 Conclusion
- Acknowledgments
- References
- Chapter Sixteen: Mass cytometry as a tool in target validation and drug discovery
- Abstract
- Abbreviations
- 1 Introduction
- 2 The CyTOF® instruments
- 3 Preparing a mass cytometry experiment for drug discovery
- 4 Mass cytometry experiments
- 5 Safety information
- References
- Edition: 1
- Volume: 690
- Published: October 17, 2023
- No. of pages (Hardback): 598
- No. of pages (eBook): 412
- Imprint: Academic Press
- Language: English
- Hardback ISBN: 9780443158711
- eBook ISBN: 9780443158728
ML
Matthew Lloyd
Dr. Matthew Lloyd is a Senior Lecturer at Department of Pharmacy & Pharmacology, Centre for Biosensors, Bioelectronics and Biodevices (C3Bio) of University of Bath, United Kingdom. He completed his Bachelor of Science at the University of Leicester, and his Doctor of Philosophy at the University of Oxford. His research is concentrated in the areas of chemical biology, enzymology, enzyme kinetics, drug discovery and cancer research.
Affiliations and expertise
Senior Lecturer, Department of Pharmacy and Pharmacology, Centre for Biosensors, Bioelectronics and Biodevices (C3Bio), University of Bath, UKRead Modern Methods of Drug Design and Development on ScienceDirect