Protein surface recognition: approaches for drug discovery

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;and, 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 INDICE: Preface List of Contributors SECTION A. PRINCIPLES 1 The discoveryand characterization of protein-protein interactions C. Bertoncini, A. Higueruelo, and Xavi Salvatella 2 Biophysics of protein-protein interactions Irene Luque SECTION B. APPROACHES 3 On the logic of natural product binding in protein-protein interactivity James J. La Clair 4 Interface peptide inhibitors of PPIs Mark W. Peczuh, and Richard T. Desmond 5 Inhibition of protein-protein interactions by peptide mimics Jorge Becerril, Johanna M. Rodriguez, Pauline N. Wyrembak, and Andrew D. Hamilton 6 Discovery of inhibitors of protein-protein interactions by screening chemical libraries Carlos García-Echeverría SECTION C.TECHNIQUES 7 High-throughput methods of chemical synthesis applied to the Preparation of inhibitors of protein-protein interactions Annaliese K. Franz, Jared T. Shaw, and Yuchen Tang 8 In silico screening F.J. Luque, and Xavier Barril 9.1 In vitro and in vivo screening: Screening by Nuclear Magnetic Resonance Ernest Giralt 9.2 In vitro and in vivo screening: Methods of High Throughput Screening Wenjiao Song and Qing Lin SECTION D. CASE STUDIES 10 Case Study: Inhibitors of the MDM2-p53 protein-protein interaction Sanjeev Shangary, Denzil Bernard, and Shaomeng Wang 11 Case Study: The Discovery of Potent LFA-1 Antagonists Tom Gadek Index

• ISBN: 978-0-470-05905-0
• Editorial: John Wiley & Sons
• Encuadernacion: Cartoné
• Páginas: 344
• Fecha Publicación: 05/11/2010
• Nº Volúmenes: 1
• Idioma: Inglés