Fragment-based Approaches in Drug Discovery provides essential information that was previously unavailable.
The book is clearly includes sections on:
- ligand design
- spectroscopic techniques
- screening and drug discovery
- numerous case studies
Fragment-based Approaches in Drug Discovery represents a book by professionals for professionals, tailor-made for drug developers in the pharma and biotech sector who need to keep up-to-date on the latest technologies and strategies in pharmaceutical ligand design.
Contents
Concept and Theory
The Concept of Fragment-based Drug Discovery
- Starting Small: Key Features of Fragment-based Ligand Design
- Historical Development
- Scope and Overview of this Book
Multivalency in Ligand Design
- Introduction and Overview
- Definitions of Terms
- Selection of Key Experimental Studies
- Theoretical Considerations in Multivalency
- Representative Experimental Studies
- Design Rules for Multivalent Ligands
- Extensions of Multivalency to Lead Discovery
- Challenges and Unsolved Problems in Multivalency
Entropic Consequences of Linking Ligands
- Rigid Body Barrier to Binding.
- Decomposition of Free Energy of Binding
- Theoretical Treatment of the Rigid Body Barrier to Binding
- Theoretical Treatment of Fragment Linking
- Experimental Examples of Fragment Linking Suitable for Analysis
- Estimate of Rigid Body Barrier to Binding
Location of Binding Sites on Proteins by the Multiple Solvent Crystal Structure Method
- Solvent Mapping
- Characterization of Protein–Ligand Binding Sites
- Functional Characterization of Proteins
- Experimental Methods for Locating the Binding Sites of Organic Probe Molecules
- Structures of Elastase in Nonaqueous Solvents
- Organic Solvent Binding Sites
- Other Solvent Mapping Experiments
- Binding of Water Molecules to the Surface of a Protein
- Internal Waters
- Surface Waters
- Conservation of Water Binding Sites
- General Properties of Solvent and Water Molecules on the Protein
- Computational Methods
Fragment Library Design and Computional Approaches
Cheminformatics Approaches to Fragment-based Lead Discovery
- The Chemical Space of Small Molecules (Under 300 a.m.u.)
- The Concept of Lead-likeness
- The Fragment-based Approach in Lead Discovery
- Literature-based Identification of Fragments: A Practical Example
Structural Fragments in Marketed Oral Drugs
- Historical Look at the Analysis of Structural Fragments of Drugs
- Methodology Used in this Analysis
- Analysis of Similarities of Different Drug Data Sets Based on the Fragment Frequencies
Fragment Docking to Proteins with the Multi-copy Simultaneous Search Methodology
- The MCSS Method
- MCSS in Practice: Functionality Maps of Endothiapepsin
- Comparison with GRID
- Comparison with Experiment
- Ligand Design with MCSS
- Protein Flexibility and MCSS
Experimental Techniques and Applications
NMR-guided Fragment Assembly
- Historical Developments Leading to NMR-based Fragment Assembly
- Theoretical Foundation for the Linking Effect
- NMR-based Identification of Fragments that Bind Proteins
- NMR-based Screening for Fragment Binding
- NMR-guided Fragment Assembly
- Combinatorial NMR-based Fragment Assembly
- Summary and Future Prospects
SAR by NMR: An Analysis of Potency Gains Realized Through Fragmentlinking and Fragment-elaboration Strategies for Lead Generation
- SAR by NMR
- Energetic Analysis of Fragment Linking Strategies
- Fragment Elaboration
- Energetic Analysis of Fragment Elaboration Strategies
Pyramid: An Integrated Platform for Fragment-based Drug Discovery
- The Pyramid Process.
- Pyramid Evolution – Integration of Crystallography and NMR.
Fragment-based Lead Discovery and Optimization Using X-Ray Crystallography, Computational Chemistry, and High-throughput Organic Synthesis
- Overview of the SGX Structure-driven Fragment-based Lead Discovery Process
- Fragment Library Design for Crystallographic Screening
- Crystallographic Screening of the SGX Fragment Library
- Complementary Biochemical Screening of the SGX Fragment Library
- Importance of Combining Crystallographic and Biochemical Fragment Screening
- Selecting Fragments Hits for Chemical Elaboration
- Fragment Optimization
- Discussion and Conclusions
- Postscript: SGX Oncology Lead Generation Program
Synergistic Use of Protein Crystallography and Solution-phase NMR Spectroscopy in Structure-based Drug Design: Strategies and Tactics
- Human Protein Tyrosine Phosphatase
- MurF
Ligand SAR Using Electrospray Ionization Mass Spectrometry
- ESI-MS of Protein and RNA Targets
- Ligands Selected Using Affinity Chromatography
- Direct Observation of Ligand–Target Complexes
- Unique Features of ESI-MS Information for Designing Ligands
Tethering
- Energetics of Fragment Selection in Tethering
- Practical Considerations.
- Finding Fragments
- Linking Fragments
- Beyond Traditional Fragment Discovery
- Related Approaches
Emerging Technologies in Chemistry
Click Chemistry for Drug Discovery
- Click Chemistry Reactions
- Click Chemistry in Drug Discovery
- In Situ Click Chemistry
- Bioconjugation Through Click Chemistry
Dynamic Combinatorial Diversity in Drug Discovery
- Dynamic Combinatorial Chemistry –The Principle
- Generation of Diversity: DCC Reactions and Building Blocks
- DCC Methodologies
- Application of DCC to Biological Systems
Index
to see books • videos • cd-roms of related interest