LEADER 05395nam 2200661Ia 450 001 9910144273603321 005 20170816122630.0 010 $a1-280-72281-9 010 $a9786610722815 010 $a3-527-60876-1 010 $a3-527-60860-5 035 $a(CKB)1000000000376655 035 $a(EBL)481418 035 $a(OCoLC)85821120 035 $a(SSID)ssj0000157791 035 $a(PQKBManifestationID)11149262 035 $a(PQKBTitleCode)TC0000157791 035 $a(PQKBWorkID)10139905 035 $a(PQKB)10093951 035 $a(MiAaPQ)EBC481418 035 $a(EXLCZ)991000000000376655 100 $a20060111d2006 uy 0 101 0 $aeng 135 $aur|n|---||||| 181 $ctxt 182 $cc 183 $acr 200 00$aFragment-based approaches in drug discovery$b[electronic resource] /$fedited by Wolfgang Jahnke and Daniel A. Erlanson 210 $aWeinheim $cWiley-VCH ;$a[Chichester $cJohn Wiley, distributor]$dc2006 215 $a1 online resource (393 p.) 225 1 $aMethods and principles in medicinal chemistry ;$v34 300 $aDescription based upon print version of record. 311 $a3-527-31291-9 320 $aIncludes bibliographical references and index. 327 $aFragment-based Approaches in Drug Discovery; Contents; Preface; A Personal Foreword; List of Contributors; Part I: Concept and Theory; 1 The Concept of Fragment-based Drug Discovery; 1.1 Introduction; 1.2 Starting Small: Key Features of Fragment-based Ligand Design; 1.2.1 FBS Samples Higher Chemical Diversity; 1.2.2 FBS Leads to Higher Hit Rates; 1.2.3 FBS Leads to Higher Ligand Efficiency; 1.3 Historical Development; 1.4 Scope and Overview of this Book; References; 2 Multivalency in Ligand Design; 2.1 Introduction and Overview; 2.2 Definitions of Terms 327 $a2.3 Selection of Key Experimental Studies2.3.1 Trivalency in a Structurally Simple System; 2.3.2 Cooperativity (and the Role of Enthalpy) in the "Chelate Effect"; 2.3.3 Oligovalency in the Design of Inhibitors to Toxins; 2.3.4 Bivalency at Well Defined Surfaces (Self-assembled Monolayers, SAMs); 2.3.5 Polyvalency at Surfaces of Viruses, Bacteria, and SAMs; 2.4 Theoretical Considerations in Multivalency; 2.4.1 Survey of Thermodynamics; 2.4.2 Additivity and Multivalency; 2.4.3 Avidity and Effective Concentration (C(eff)); 2.4.4 Cooperativity is Distinct from Multivalency 327 $a2.4.5 Conformational Entropy of the Linker between Ligands2.4.6 Enthalpy/Entropy Compensation Reduces the Benefit of Multivalency; 2.5 Representative Experimental Studies; 2.5.1 Experimental Techniques Used to Examine Multivalent Systems; 2.5.1.1 Isothermal Titration Calorimetry; 2.5.1.2 Surface Plasmon Resonance Spectroscopy; 2.5.1.3 Surface Assays Using Purified Components (Cell-free Assays); 2.5.1.4 Cell-based Surface Assays; 2.5.2 Examination of Experimental Studies in the Context of Theory; 2.5.2.1 Trivalency in Structurally Simple Systems 327 $a2.5.2.2 Cooperativity (and the Role of Enthalpy) in the "Chelate Effect"2.5.2.3 Oligovalency in the Design of Inhibitors of Toxins; 2.5.2.4 Bivalency in Solution and at Well Defined Surfaces (SAMs); 2.5.2.5 Polyvalency at Surfaces (Viruses, Bacteria, and SAMs); 2.6 Design Rules for Multivalent Ligands; 2.6.1 When Will Multivalency Be a Successful Strategy to Design Tight-binding Ligands?; 2.6.2 Choice of Scaffold for Multivalent Ligands; 2.6.2.1 Scaffolds for Oligovalent Ligands; 2.6.2.2 Scaffolds for Polyvalent Ligands; 2.6.3 Choice of Linker for Multivalent Ligands 327 $a2.6.3.1 Rigid Linkers Represent a Simple Approach to Optimize Affinity2.6.3.2 Flexible Linkers Represent an Alternative Approach to Rigid Linkers to Optimize Affinity; 2.6.4 Strategy for the Synthesis of Multivalent Ligands; 2.6.4.1 Polyvalent Ligands: Polymerization of Ligand Monomers; 2.6.4.2 Polyvalent Ligands: Functionalization with Ligands after Polymerization; 2.7 Extensions of Multivalency to Lead Discovery; 2.7.1 Hetero-oligovalency Is a Broadly Applicable Concept in Ligand Design; 2.7.2 Dendrimers Present Opportunities for Multivalent Presentation of Ligands 327 $a2.7.3 Bivalency in the Immune System 330 $aThis first systematic summary of the impact of fragment-based approaches on the drug development process provides essential information that was previously unavailable. Adopting a practice-oriented approach, this represents a book by professionals for professionals, tailor-made for drug developers in the pharma and biotech sector who need to keep up-to-date on the latest technologies and strategies in pharmaceutical ligand design. The book is clearly divided into three sections on ligand design, spectroscopic techniques, and screening and drug discovery, backed by numerous case studies. 410 0$aMethods and principles in medicinal chemistry ;$vv. 34. 606 $aDrug development 606 $aLigands (Biochemistry) 608 $aElectronic books. 615 0$aDrug development. 615 0$aLigands (Biochemistry) 676 $a615 676 $a615.1901 701 $aJahnke$b Wolfgang$0997913 701 $aErlanson$b Daniel A$0997914 801 0$bMiAaPQ 801 1$bMiAaPQ 801 2$bMiAaPQ 906 $aBOOK 912 $a9910144273603321 996 $aFragment-based approaches in drug discovery$92288667 997 $aUNINA