{"product_id":"protein-surface-recognition-isbn-9780470059050","title":"Protein Surface Recognition","description":"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.  \u003cp\u003e\u003ci\u003eProtein Surface Recognition\u003c\/i\u003e presents a detailed treatment of this strategy, with topics including:\u003c\/p\u003e \u003cul\u003e \u003cli\u003ean 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\u003c\/li\u003e \u003cli\u003ethe fundamental physical issues that surround protein-protein interactions that must be considered when designing ligands for protein surfaces\u003c\/li\u003e \u003cli\u003eexamples 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\u003c\/li\u003e \u003cli\u003ea 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 \u003ci\u003ein silico\u003c\/i\u003e and \u003ci\u003ein vitro\u003c\/i\u003e methods for the discovery of novel protein ligands.\u003c\/li\u003e \u003c\/ul\u003e \u003cp\u003e\u003ci\u003eProtein Surface Recognition\u003c\/i\u003e provides an intellectual “tool-kit” for investigators in medicinal and bioorganic chemistry looking to exploit this emerging paradigm in drug discovery.\u003c\/p\u003e  Preface.  \u003cp\u003eList of Contributors.\u003c\/p\u003e \u003cp\u003e\u003cb\u003ePART I PRINCIPLES.\u003c\/b\u003e\u003c\/p\u003e \u003cp\u003e\u003cb\u003e1\u003c\/b\u003e \u003cb\u003eThe Discovery and Characterization of Protein-Protein Interactions\u003c\/b\u003e (\u003ci\u003eC.W. Bertoncini, A. Higueruelo, and X. Salvatella\u003c\/i\u003e).\u003c\/p\u003e \u003cp\u003e1.1 Introduction.\u003c\/p\u003e \u003cp\u003e1.2 Techniques to Identify Protein-Protein Interactions.\u003c\/p\u003e \u003cp\u003e1.3 Techniques to Characterize Protein-Protein Interactions.\u003c\/p\u003e \u003cp\u003e1.4 Structure and Dynamics of Protein Complexes.\u003c\/p\u003e \u003cp\u003e1.5 Protein-Protein Complexes as Therapeutic Targets.\u003c\/p\u003e \u003cp\u003e1.6 Conclusions.\u003c\/p\u003e \u003cp\u003eReferences.\u003c\/p\u003e \u003cp\u003e\u003cb\u003e2 Biophysics of Protein-Protein Interactions\u003c\/b\u003e (\u003ci\u003eIrene Luque\u003c\/i\u003e).\u003c\/p\u003e \u003cp\u003e2.1 Introduction.\u003c\/p\u003e \u003cp\u003e2.2 Intermolecular Forces in Protein Recognition.\u003c\/p\u003e \u003cp\u003e2.3 Basic Binding Thermodynamics.\u003c\/p\u003e \u003cp\u003e2.4 Thermodynamically Driven Drug Design.\u003c\/p\u003e \u003cp\u003e2.5 Measurement of Binding Energetics.\u003c\/p\u003e \u003cp\u003e2.6 Structure-based Calculation of Protein Binding Energetics.\u003c\/p\u003e \u003cp\u003e2.7 Interfacial Water Molecules in Protein Recognition.\u003c\/p\u003e \u003cp\u003e2.8 The Linkage Between Binding and Conformational Equilibrium in Proteins.\u003c\/p\u003e \u003cp\u003eReferences.\u003c\/p\u003e \u003cp\u003e\u003cb\u003ePART II APPROACHES.\u003c\/b\u003e\u003c\/p\u003e \u003cp\u003e\u003cb\u003e3 On the Logic of Natural Product Binding in Protein-Protein Interactivity\u003c\/b\u003e (\u003ci\u003eJames J. La Clair\u003c\/i\u003e).\u003c\/p\u003e \u003cp\u003e3.1 Introduction.\u003c\/p\u003e \u003cp\u003e3.2 Structural Logic.\u003c\/p\u003e \u003cp\u003e3.3 Functional Logic.\u003c\/p\u003e \u003cp\u003e3.4 The Need for Programmers.\u003c\/p\u003e \u003cp\u003e3.5 Compiling the NPPI Mapper.\u003c\/p\u003e \u003cp\u003eReferences.\u003c\/p\u003e \u003cp\u003e\u003cb\u003e4 Interface peptide inhibitors of PPIs\u003c\/b\u003e (\u003ci\u003eMark W. Peczuh, and Richard T. Desmond\u003c\/i\u003e).\u003c\/p\u003e \u003cp\u003e4.1 Interface Peptides Defined.\u003c\/p\u003e \u003cp\u003e4.2 Unmodified Peptides.\u003c\/p\u003e \u003cp\u003e4.3 Modified Peptides.\u003c\/p\u003e \u003cp\u003e4.4 Summary\/Perspective.\u003c\/p\u003e \u003cp\u003eReferences.\u003c\/p\u003e \u003cp\u003e\u003cb\u003e5\u003c\/b\u003e \u003cb\u003eInhibition of Protein-Protein Interactions by Peptide Mimics\u003c\/b\u003e (\u003ci\u003eJorge Becerril, Johanna M. Rodriguez, Pauline N. Wyrembak, and Andrew D. Hamilton\u003c\/i\u003e).\u003c\/p\u003e \u003cp\u003e5.1 Introduction.\u003c\/p\u003e \u003cp\u003e5.2 Inhibition of Calmodulin.\u003c\/p\u003e \u003cp\u003e5.3 Inhibition of HIV-1 Fusion.\u003c\/p\u003e \u003cp\u003e5.4 Inhibition of the Nuclear Estrogen Receptor.\u003c\/p\u003e \u003cp\u003e5.5 Inhibition of the Bcl-x\u003csub\u003e\u003csmall\u003eL\u003c\/small\u003e\u003c\/sub\u003e\/Bak Interaction.\u003c\/p\u003e \u003cp\u003e5.6 Inhibition of the p53\/MDM2 Interaction.\u003c\/p\u003e \u003cp\u003e5.7 Miscellaneous Protein Targets.\u003c\/p\u003e \u003cp\u003e5.8 Conclusion.\u003c\/p\u003e \u003cp\u003eReferences.\u003c\/p\u003e \u003cp\u003e\u003cb\u003e6\u003c\/b\u003e \u003cb\u003eDiscovery of Inhibitors of Protein-Protein Interactions by Screening Chemical Libraries\u003c\/b\u003e (\u003ci\u003eCarlos García-Echeverría\u003c\/i\u003e).\u003c\/p\u003e \u003cp\u003e6.1 Introduction.\u003c\/p\u003e \u003cp\u003e6.2 Screening Strategies to Identify and Develop Antagonists of Protein-Protein Interactions.\u003c\/p\u003e \u003cp\u003e6.3 Mimetics of Common Protein Structure Motifs and Structure-based Design of Peptidomimetics.\u003c\/p\u003e \u003cp\u003e6.4 Conclusions and Outlook.\u003c\/p\u003e \u003cp\u003eReferences.\u003c\/p\u003e \u003cp\u003e\u003cb\u003ePART III TECHNIQUES.\u003c\/b\u003e\u003c\/p\u003e \u003cp\u003e\u003cb\u003e7\u003c\/b\u003e \u003cb\u003eHigh-throughput Methods of Chemical Synthesis Applied to the Preparation of Inhibitors of Protein-Protein Interactions\u003c\/b\u003e (\u003ci\u003eAnnaliese K. Franz, Jared T. Shaw, and Yuchen Tang\u003c\/i\u003e).\u003c\/p\u003e \u003cp\u003e7.1 Introduction.\u003c\/p\u003e \u003cp\u003e7.2 Survey of High-throughput Organic Synthesis.\u003c\/p\u003e \u003cp\u003e7.3 Synthesis of 'Peptide-Inspired' Compounds and Libraries.\u003c\/p\u003e \u003cp\u003e7.4 Synthesis of 'Natural Product-Inspired' Compounds and Libraries.\u003c\/p\u003e \u003cp\u003e7.5 Diversity Oriented Synthesis (DOS) in the Discovery of PPI Inhibitors.\u003c\/p\u003e \u003cp\u003e7.6 Summary and Outlook.\u003c\/p\u003e \u003cp\u003eReferences.\u003c\/p\u003e \u003cp\u003e\u003cb\u003e8 \u003ci\u003eIn Silico\u003c\/i\u003e screening\u003c\/b\u003e (\u003ci\u003eF.J. Luque, and Xavier Barril\u003c\/i\u003e).\u003c\/p\u003e \u003cp\u003e8.1 Introduction.\u003c\/p\u003e \u003cp\u003e8.2 Methods for Virtual Ligand Screening.\u003c\/p\u003e \u003cp\u003e8.3 Binding Site Characterization.\u003c\/p\u003e \u003cp\u003e8.4 Case Studies.\u003c\/p\u003e \u003cp\u003e8.5 Outlook and Conclusions.\u003c\/p\u003e \u003cp\u003eReferences.\u003c\/p\u003e \u003cp\u003e\u003cb\u003e9.1\u003c\/b\u003e \u003cb\u003e\u003ci\u003eIn Vitro\u003c\/i\u003e Screening: Screening by Nuclear Magnetic Resonance\u003c\/b\u003e (\u003ci\u003eErnest Giralt\u003c\/i\u003e).\u003c\/p\u003e \u003cp\u003e9.1.1 Saturation Transfer Difference (STD).\u003c\/p\u003e \u003cp\u003e9.1.2 STD in Fragment-based Drug Design.\u003c\/p\u003e \u003cp\u003e9.1.3 Chemical Shift Perturbation (CSP).\u003c\/p\u003e \u003cp\u003e9.1.4 \u003csup\u003e\u003csmall\u003e19\u003c\/small\u003e\u003c\/sup\u003eF-NMR in Molecular Recognition Studies.\u003c\/p\u003e \u003cp\u003eReferences.\u003c\/p\u003e \u003cp\u003e\u003cb\u003e9.2 \u003ci\u003eIn Vitro\u003c\/i\u003e Screening: Methods of High-throughput Screening\u003c\/b\u003e (\u003ci\u003eWenjiao Song and Qing Lin\u003c\/i\u003e).\u003c\/p\u003e \u003cp\u003e9.2.1 Introduction.\u003c\/p\u003e \u003cp\u003e9.2.2 Statistical Evaluation of the HTS Assay Performance.\u003c\/p\u003e \u003cp\u003e9.2.3 Biochemical Assays.\u003c\/p\u003e \u003cp\u003e9.2.4 Cell-based Assays.\u003c\/p\u003e \u003cp\u003e9.2.5 Conclusion.\u003c\/p\u003e \u003cp\u003eReferences.\u003c\/p\u003e \u003cp\u003e\u003cb\u003ePART IV CASE STUDIES.\u003c\/b\u003e\u003c\/p\u003e \u003cp\u003e\u003cb\u003e10 Case Study: Inhibitors of the MDM2-p53 Protein-Protein Interaction\u003c\/b\u003e (\u003ci\u003eSanjeev Shangary, Denzil Bernard, and Shaomeng Wang\u003c\/i\u003e).\u003c\/p\u003e \u003cp\u003e10.1 MDM2-p53 Protein-Protein Interaction: A Case Study.\u003c\/p\u003e \u003cp\u003e10.2 Regulation of p53 by the MDM2-p53 Protein-Protein Interaction.\u003c\/p\u003e \u003cp\u003e10.3 Structural Basis of the MDM2-p53 Interaction.\u003c\/p\u003e \u003cp\u003e10.4 Design of p53-based Peptides.\u003c\/p\u003e \u003cp\u003e10.5 Design of Nonpeptidic Small-Molecule Inhibitors of the MDM2-p53 Interaction.\u003c\/p\u003e \u003cp\u003e10.6 Challenges in the Design of Small Molecule Inhibitors of the MDM2-p53 Interaction.\u003c\/p\u003e \u003cp\u003e10.7 Reactivation of p53 by Inhibitors of the MDM2-p53 Interaction.\u003c\/p\u003e \u003cp\u003e10.8 Development of MDM2 Inhibitors and New Anticancer Drugs.\u003c\/p\u003e \u003cp\u003e10.9 Concluding Remarks.\u003c\/p\u003e \u003cp\u003eReferences.\u003c\/p\u003e \u003cp\u003e\u003cb\u003e11 Case Study: The Discovery of Potent LFA-1 Antagonists\u003c\/b\u003e (\u003ci\u003eTom Gadek\u003c\/i\u003e).\u003c\/p\u003e \u003cp\u003e11.1 Introduction.\u003c\/p\u003e \u003cp\u003e11.2 Structural, Molecular and Cellular Biologies of LFA-1.\u003c\/p\u003e \u003cp\u003e11.3 The Search for Small Molecule LFA-1 Antagonists.\u003c\/p\u003e \u003cp\u003e11.4 Screening Assays.\u003c\/p\u003e \u003cp\u003e11.5 Lead Identification and Optimization.\u003c\/p\u003e \u003cp\u003e11.6 Protein and Small Molecule Structure Activity Relationships (PSAR) in the LFA-1\/ICAM-1 Interaction.\u003c\/p\u003e \u003cp\u003e11.7 Summary.\u003c\/p\u003e \u003cp\u003eReferences.\u003c\/p\u003e \u003cp\u003eIndex.\u003c\/p\u003e  \"This book picks up this trend and provides an excellent overview of the current topics in the field of PPI modulation by small molecules and peptides. . . Taken together, this excellent book is very suitable both as an introduction to the field, as well as a compendium for readers already familiar with the chemical approach of modulating PPIs.\" (ChemMedChem, 2011)  \u003cp\u003e \u003c\/p\u003e  \u003cb\u003eERNEST GIRALT,\u003c\/b\u003e Department of Organic Chemistry, University of Barcelona and Institute for Research in Biomedicine, Barcelona, Spain  \u003cp\u003e\u003cb\u003eMARK PECZUH,\u003c\/b\u003e Department of Chemistry, University of Connecticut, USA\u003c\/p\u003e \u003cp\u003e\u003cb\u003eXAVIER SALVATELLA,\u003c\/b\u003e ICREA and Institute for Research in Biomedicine, Barcelona, Spain\u003c\/p\u003e  \u003cb\u003e\u003ci\u003eProtein Surface Recognition: Approaches for Drug Discovery\u003c\/i\u003e\u003c\/b\u003e  \u003cp\u003eA 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 (PPIs). 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.\u003c\/p\u003e \u003cp\u003e\u003ci\u003eProtein Surface Recognition: Approaches for Drug Discovery\u003c\/i\u003e presents a detailed treatment of this strategy. Starting with a survey of PPIs that are key players in human disease and biology and the potential for therapeutics derived from this new perspective, the book then examines 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 are given. Finally, the book surveys 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, and ends with two extended case studies - inhibitors of the MDM2-p53 PPI, and the discovery of potent LFA-1 antagonists.\u003c\/p\u003e \u003cp\u003e\u003ci\u003eProtein Surface Recognition: Approaches for Drug Discovery\u003c\/i\u003e provides an intellectual ‘tool-kit' for investigators in medicinal and bioorganic chemistry looking to exploit this emerging paradigm in drug discovery.\u003c\/p\u003e","brand":"Wiley","offers":[{"title":"Default Title","offer_id":47989880422629,"sku":"NP9780470059050","price":169.95,"currency_code":"USD","in_stock":false}],"thumbnail_url":"\/\/cdn.shopify.com\/s\/files\/1\/1842\/7735\/files\/9780470059050.jpg?v=1761785773","url":"https:\/\/k12savings.com\/es\/products\/protein-surface-recognition-isbn-9780470059050","provider":"K12savings","version":"1.0","type":"link"}