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Informationen zum Autor 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 Klappentext 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. Zusammenfassung 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. Inhaltsverzeichnis Preface. List of Contributors. PART I PRINCIPLES. 1 The Discovery and Characterization of Protein-Protein Interactions ( C.W. Bertoncini, A. Higueruelo, and X. Salvatella ). 1.1 Introduction. 1.2 Techniques to Identify Protein-Protein Interactions. 1.3 Techniques to Characterize Protein-Protein Interactions. 1.4 Structure and Dynamics of Protein Complexes. 1.5 Protein-Protein Complexes as Therapeutic Targets. 1.6 Conclusions. References. 2 Biophysics of Protein-Protein Interactions ( Irene Luque ). 2.1 Introduction. 2.2 Intermolecular Forces in Protein Recognition. 2.3 Basic Binding Thermodynamics. 2.4 Thermodynamically Driven Drug Design. 2.5 Measurement of Binding Energetics. 2.6 Structure-based Calculation of Protein Binding Energetics. 2.7 Interfacial Water Molecules in Protein Recognition. 2.8 The Linkage Between Binding and Conformational Equilibrium in Proteins. References. PART II APPROACHES. 3 On the Logic of Natural Product Binding in Protein-Protein Interactivity ( James J. La Clair ). 3.1 Introduction. 3.2 Structural Logic. 3.3 Functional Logic. 3.4 The Need for Programmers. 3.5 Compiling the NPPI Mapper. References. 4 Interface peptide inhibitors of PPIs ( Mark W. Peczuh, and Richard T. Desmond ). 4.1 Interface Peptides Defined. 4.2 Unmodified Peptides. 4.3 Modified Peptides. 4.4 Summary/Perspective. References. 5 Inhibition of Protein-Protein Interactions by Peptide Mimics ( Jorge Becerril, Johanna M. Rodriguez, Pauline N. Wyrembak, and...
