Amino Acids, Peptides and Proteins in Organic Chemistry Building Blocks, Catalysis and Coupling Chemistry

Andrew Hughes is a reader and Head of the Department of Chemistry, La Trobe University, Melbourne, Australia. He obtained his degrees from the University of Western Australia before taking up post-doctoral appointments at the University of Cambridge starting 1989. After three years working with Professor Andrew Holmes, he joined Professor Steven Ley´s group. While at Cambridge he was appointed the Shell Research Fellow at Robinson College. His interests lie in the general field of asymmetric synthesis and methodology, with a recent focus on amino acid chemistry.

Diese praxisbezogene Reihe 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.

Closing a gap in the literature, this practical book series in 5 volumes draws on the expertise of the "who s who" in amino acid research to provide a comprehensive discussion of the occurrence, uses and applications of amino acids, their polymeric forms, peptides and proteins.
.

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 Transformations for Cys-Free Ligations in Peptides and ProteinsOther Chemoselective Capture StrategiesPeptide Ligations by Chemoselective Amide-Bond-Forming ReactionsStrategies for the Ligation of Multiple FragmentsAUTOMATION OF PEPTIDE SYNTHESISIntroductionSPPS: From Mechanization to AutomationDeprotection Step: Monitoring and ControlCoupling Step: Monitoring and ControlIntegrated Deprotection and Coupling ControlPEPTIDE PURIFICATION BY REVERSED-PHASE CHROMATOGRAPHYRP-HPLC of PeptidesPeptide PropertiesChromatographic PrinciplesPrediction of Peptide Retention TimesAdvantages of Reduced ScaleTwo-Dimensional Chromatographic MethodsPeptide Analysis in Complex Biological MatricesStandard Methods for Peptide Separations for Analysis by Hyphenated TechniquesEmerging Methods for Peptide Separations for Analysis by Hyphenated TechniquesPractical Use of RP-HPLC for Purifying Peptides (Analytical and Preparative Scale)DIFFICULT PEPTIDESImportance of Peptide SynthesisMethods for Peptide SynthesisChemical Peptide Synthesis"Difficult Peptide Sequences"Means to Overcome Peptide Aggregation in SPPSMonitoring the Synthesis of a "Difficult Peptide"Conclusions