Amino Acids, Peptides and Proteins in Organic Chemistry

This is the third of five books in the Amino Acids, Peptides and Proteins in Organic Synthesis series. Closing a gap in the literature, this is the only series to cover this important topic in organic and biochemistry. Drawing upon the combined expertise of the international "e;who's who"e; in amino acid research, these volumes represent a real benchmark for amino acid chemistry, providing a comprehensive discussion of the occurrence, uses and applications of amino acids and, by extension, their polymeric forms, peptides and proteins. The practical value of each volume is heightened by the inclusion of experimental procedures. The 5 volumes cover the following topics: Volume 1: Origins and Synthesis of Amino Acids Volume 2: Modified Amino Acids, Organocatalysis and Enzymes Volume 3: Building Blocks, Catalysis and Coupling Chemistry Volume 4: Protection Reactions, Medicinal Chemistry, Combinatorial Synthesis Volume 5: Analysis and Function of Amino Acids and Peptides This third volume in the series presents an in depth account of recent developments in the (bio-)synthesis of amino acids and peptides. Divided into two parts, the first section deals with amino acids as building blocks, including the generation of alpha-amino acids, beta-lactams, and heterocycles. The second section is devoted to the synthesis of peptides, with the focus on solid phase synthesis. However, solution phase peptide synthesis is covered as well, as are topics such as coupling reagents, chemical ligation, peptide purification and automation. Originally planned as a six volume series, Amino Acids, Peptides and Proteins in Organic Chemistry now completes with five volumes but remains comprehensive in both scope and coverage. Further information about the 5 Volume Set and purchasing details can be viewed here.

Diese praxisbezogene Reihe in 5 Bänden stützt sich auf Wissen und Erfahrungen der weltweit bedeutendsten Aminosäure-Forscher. Mit ihrer ausführlichen Diskussion von Vorkommen, Nutzen und Anwendungsbeispielen von Aminosäuren und ihren Polymeren (Peptiden und Proteinen) schließt sie eine Lücke in der Literatur.

PART I: Amino Acids as Building BlocksAMINO ACID BIOSYNTHESISIntroductionGlutamate and Glutamine: Gateways to Amino Acid BioynthesisOther Amino Acids from Ubiquitous Metabolites: Pyridoxal Phosphate-Dependent Routes to Aspartate, Alanine, and GlycineRoutes to Functionalized Three-Carbon Amino Acids: Serine, Cysteine, and SelenocysteineOther Amino Acids fron Aspartate and Glutamate: Asparagine and Side Chain Functional Group ManipulationAspartate and Glutamate Families of Amino AcidsBiosynthesis of Aliphatic Amino Acids with Modified Carbon Skeletons: Branched-Chain Amino Acids, Lysine, and PyrrolysineBiosynthesis of the Aromatic Amino AcidsConclusionsHETEROCYCLES FROM AMINO ACIDSIntroductionHeterocycles Generated by Intramolecular CyclizationsHeterocycles Generated by Intermolecular CyclizationsHeterocycles Generated by CycloadditionsConclusionsExperimental ProceduresRADICAL-MEDIATED SYNTHESIS OF ALPHA-AMINO ACIDS AND PEPTIDESIntroductionFree Radical ReactionsRadical Addition to Imine DerivativesRadical Conjugate AdditionConclusionsExperimental ProtocolsSYNTHESIS OF BETA-LACTAMS (CEPHALOSPORINS) BY BIOCONVERSIONIntroductionBiosynthetic Pathways of Cephalosporins and PenicillinsProduction of 7-ACA by A. chrysogenumProduction of 7-ADCA by A. chrysogenumProduction of Penicillin G by A. chrysogenumProduction of Cephalosporins by P. chrysogenumConversion of Penicillin G and other Penicillins to DAOG by Streptomyces clavuligerusConclusionsSTRUCTURE AND REACTIVITY OF BETA-LACTAMSIntroductionStructureReactivityHydrolysisAminolysisEpimerizationPART II: Amino Acid Coupling ChemistrySOLUTION-PHASE PEPTIDE SYNTHESISPrinciple of Peptide SynthesisProtection ProceduresChain Elongation ProceduresFinal Deprotection MethodsSOLID-PHASE PEPTIDE SYNTHESIS: HISTORICAL ASPECTSIntroductionSelection of Compatible Synthetic ComponentsRacemization and Stepwise Peptide AssemblyOptimization of Synthetic ComponentsForeshadowing of the Nobel PrizeAutomation of SPPSImpact of New Protecting Groups and Resin LinkagesSolid-Phase Organic ChemistryEarly Applications of SPPS to Small ProteinsSide-Reactions and Sequence-Dependent ProblemsRapid Expansion of Usage Leading to the Nobel PrizeFrom the Nobel Prize Forward to Combinatorial ChemistryProtein Synthesis and Peptide LigationConclusionsLINKERS FOR SOLID-PHASE PEPTIDE SYNTHESISIntroductionImmobilization via Carboxyl GroupImobilization via Amino GroupBackbone ImmobilizationImmobilization via Amino Acid Side-ChainConclusionsORTHOGONAL PROTECTING GROUPS AND SIDE-REACTIONS IN Fmoc/tBu SOLID-PHASE PEPTIDE SYNTHESISOrthogonal Protecting Groups in Fmoc/tBu Solid-Phase Peptide SynthesisSide-Reactions in Fmoc/tBu Solid-Phase Peptide SynthesisFmoc METHODOLOGY: CLEAVAGE FROM THE RESIN AND FINAL DEPROTECTIONIntroduction"Low" TFA-Labile Resins"High" TFA-Labile ResinsFinal RemarksSTRATEGY IN SOLID-PHASE PEPTIDE SYNTHESISSynthetic Strategies Utilizing Solid-Phase Peptide Synthesis MethodsSolid Support: Resins and LinkersDeveloping the Synthetic Strategy: Selection of the Protecting Group SchemeResin LoadingSBS Peptide Chain Elongation: Coupling and ActivationPiperazine FormationSolid-Phase Synthesis of Protected Peptide SegmentsFragment Condensation Approach: Convergent and Hybrid SyntesesCleavage from the Resin and Global Peptide DeprotectionDisulfide Bond-Containing PeptidesNative Chemical Ligation (NCL)SPPS of Peptides Modified at their C-TerminusSide-Chain-Modified PeptidesCyclic PeptidesLarge-Scale Solid-Phase SynthesisConclusionsPEPTIDE-COUPLING REAGENTSIntroductionCarbodiimidesPhosphonium SaltsAminium/Uronium SaltsFluoroformamidinium Coupling ReagentsOrganophosphorus ReagentsTriazine Coupling ReagentsMukaiyama's ReagentConclusionsCHEMOSELECTIVE PEPTIDE LIGATION: A PRIVILEGED TOOL FOR PROTEIN SYNTHESISIntroductionChemoselective Peptide Ligations Following a Capture/Rearrangement StrategyChemical Transf