Protein Surface Recognition Approaches for

A new perspective on the design of molecular therapeutics is emerging. This new strategy emphasizes the rational complementation of functionality along extended patches of a protein surface with the aim of inhibiting protein/protein interactions. The successful development of compounds able to inhibit these interactions offers a unique chance to selectively intervene in a large number of key cellular processes related to human disease.Protein Surface Recognition presents a detailed treatment of this strategy, with topics including: an extended survey of protein-protein interactions that are key players in human disease and biology and the potential for therapeutics derived from this new perspective the fundamental physical issues that surround protein-protein interactions that must be considered when designing ligands for protein surfaces examples of protein surface-small molecule interactions, including treatments of protein-natural product interactions, protein-interface peptides, and rational approaches to protein surface recognition from model to biological systems a survey of techniques that will be integral to the discovery of new small molecule protein surface binders, from high throughput synthesis and screening techniques to in silico and in vitro methods for the discovery of novel protein ligands.Protein Surface Recognition provides an intellectual "tool-kit" for investigators in medicinal and bioorganic chemistry looking to exploit this emerging paradigm in drug discovery.

ERNEST GIRALT, Department of Organic Chemistry, University of Barcelona and Institute for Research in Biomedicine, Barcelona, Spain

MARK PECZUH, Department of Chemistry, University of Connecticut, USA

XAVIER SALVATELLA, ICREA and Institute for Research in Biomedicine, Barcelona, Spain

Preface
List of Contributors
Principles
The discovery and characterization of protein-protein interactions
Biophysics of protein-protein interactions
Approaches
On the logic of natural product binding in protein-protein interactivity
Interface peptide inhibitors of PPIs
Inhibition of protein-protein interactions by peptide mimics
Discovery of inhibitors of protein-protein interactions by screening chemical libraries
Techniques
High-throughput methods of chemical synthesis applied to the Preparation of inhibitors of protein-protein interactions
In silico screening
In vitro and in vivo screening: Screening by Nuclear Magnetic Resonance
In vitro and in vivo screening: Methods of High Throughput Screening
Case Studies
Case Study: Inhibitors of the MDM2-p53 protein-protein interaction
Case Study: The Discovery of Potent LFA-1 Antagonists
Index
Table of Contents provided by Publisher. All Rights Reserved.

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Protein Surface Recognition Approaches for Drug Discovery

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Table of Contents

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