Drug Design and Discovery book from C.H.I.P.S.

Fragment-based Approaches in Drug Discovery
by Wolfgang Jahnke

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.


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


  • 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


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Fragment-based Approaches in Drug Discovery
by Wolfgang Jahnke
2006 • 369 pages • $214.00 + shipping
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