05395nam 2200661Ia 450 991014427360332120170816122630.01-280-72281-997866107228153-527-60876-13-527-60860-5(CKB)1000000000376655(EBL)481418(OCoLC)85821120(SSID)ssj0000157791(PQKBManifestationID)11149262(PQKBTitleCode)TC0000157791(PQKBWorkID)10139905(PQKB)10093951(MiAaPQ)EBC481418(EXLCZ)99100000000037665520060111d2006 uy 0engur|n|---|||||txtccrFragment-based approaches in drug discovery[electronic resource] /edited by Wolfgang Jahnke and Daniel A. ErlansonWeinheim Wiley-VCH ;[Chichester John Wiley, distributor]c20061 online resource (393 p.)Methods and principles in medicinal chemistry ;34Description based upon print version of record.3-527-31291-9 Includes bibliographical references and index.Fragment-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 Terms2.3 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 Multivalency2.4.5 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 Systems2.5.2.2 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 Ligands2.6.3.1 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 Ligands2.7.3 Bivalency in the Immune SystemThis 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.Methods and principles in medicinal chemistry ;v. 34.Drug developmentLigands (Biochemistry)Electronic books.Drug development.Ligands (Biochemistry)615615.1901Jahnke Wolfgang997913Erlanson Daniel A997914MiAaPQMiAaPQMiAaPQBOOK9910144273603321Fragment-based approaches in drug discovery2288667UNINA02091nam 2200385 n 450 99639534760331620200824121003.0(CKB)4330000000328100(EEBO)2240850658(UnM)99841219e(UnM)99841219(EXLCZ)99433000000032810019910322d1621 uy |engurbn||||a|bb|The French garden: for English ladyes and gentlewomen to walke in: or, A sommer dayes labonr [sic][electronic resource] Being an instruction for the attayning vnto the knowledge of the French tongue: wherein for the practise thereof, are framed thirteene dialogues in French and English, concerning diuers matters from the rising in the morning till bed-time. Also the historie of the centurion mentioned in the Gospell: in French verses. Which is an easier and shorter methode then hath beene yet set forth, to bring the louers of the French tongue to the perfection of the same. Newly corrected and augmented with necessary rules, by the author Peter Erondell, professor of the same language: and Iohn Fabre his adjointLondon Printed by Edw: All-de for Iohn Grismond, and are to be solde at his shop neere the little north doore of S. Paules Church, at the signe of the Gunne1621[246] pEnglish and French on facing pages.Signatures: A-P Q⁴ (-A1).Reproduction of the original in the Henry E. Huntington Library and Art Gallery.eebo-0113French languageConversation and phrase booksEnglishFrench languageGrammarEarly works to 1800French languageEnglish.French languageGrammarErondelle Pierrefl. 1586-1609.1003939Cu-RivESCu-RivESCStRLINWaOLNBOOK996395347603316The French garden: for English ladyes and gentlewomen to walke in: or, A sommer dayes labonr2387491UNISA