Protein Surface Recognition Approaches for Drug Discovery

by Giralt, Ernest; Peczuh, Mark; Salvatella, Xavier

• ISBN13: 9780470059050
• ISBN10: 0470059052
• Edition: 1st
• Format: Hardcover
• Copyright: 2010-12-01
• Publisher: Wiley

Summary

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.

Author Biography

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

Table of Contents

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

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