A Specialist Periodical Report Amino Acids and Peptides Volume 24 A Review of the Literature Published during 1991 Senior Reporter J.S. Davies, University College of Swansea Reporters G.C. Barrett, Oxford Brookes University C. M. Bl adon, Interprobe Chemical Services, Glasgo w D.T. Elmore, University of Oxford C.H. Frydrych, Beecham Pharmaceuticals SOCIETY OF CHEMISTRY ISBN 0-85 186-224- 1 ISSN 0269-752 1 0 The Royal Society of Chemistry, 1993 A II Riglr ts Reser veil No part of this hook mu!’ be reproduced or transmitted in an? fbrni or bj*a nj2 tiieans - graphic, elec tron ic , including phot ocopj*ing,r ecording, tuping, or inforrimtion storage and retrieval systems nlithout - written perniission ,fi.om the Ro~*aSlo ciety of‘C hertiistr*j* Published by the Royal Society of Chemistry Thomas Graham House, Science Park, Cambridge CB4 4WF Printed and bound in England by Athenaeum Press Ltd, Newcastle upon Tyne Preface In taking over after Dr John Jones's 10-year tenure as Senior Reporter, the philosophy has been to preserve continuity through reliance on the expertise of authors who have done this series proud over many years. The experience of having to read each author's manuscripts has highlighted again the unstinting efforts of my colleagues in reviewing such a wide 'swath' of papers and moulding them into useful treatises. Sincere thanks, therefore to Graham Barrett, Donald Elmore and Colin Frydrych for agreeing to soldier on, and to Christine Bladon for accepting and fulfilling the challenge of producing her first Chapter in this series. Continuity for the Chapter on metal complexes of amino-acids and peptides had also been planned, but pressure of work on Professors Nolan and Hay necessitated the decision to include their Chapter as a biennial contribution which will now appear next year. The year 1991 saw consolidation rather than any quantum leaps in development in most of the areas reviewed. Quite detailed probing of biological systems with high field nmr is now possible and in the field of molecular recognition involving immunosuppressive agents, it has prompted an eminent practitioner to state that "the fog is slowly lifting on the understanding of immunosuppression". Over the years, within the criteria of purity used for inclusion of peptide syntheses in these Volumes, the size of peptides have continued to increase. But the success of the solid phase approach has seen the burgeoning of techniques which enable "multiple peptide syntheses" to be carried out. 'Biologically-required' sequences are selected from the products of "multiple peptide synthesis". This will inevitably demand editorial consideration soon to ascertain whether our criteria for reviewing these developments will have to be re-defined. The trend towards larger peptides has increased the use of single letter amino acid abbreviations to report the peptide sequences. As a service to all of us who still find the occasional letter designation elusive, a list has been included in the Abbreviations section. The structures of the closely related coupling agents developed as alternatives to the BOP reagent are also included as the trend is to refer to them only by their abbreviations. Finally, sincere thanks to John Jones for his 10-year tenure and to Colin Frydrych who has intimated his wish to make this his last Chapter for the present. John S Davies University of Wales, Swansea Contents Chapter 1 Amino Acids By G. C. Barrrtt 1 Introduction 2 Textbooks and Reviews 3 Naturally Occurring Amino Acids Methodology of Isolation of Amino Acids from Natural Sources Occurrence of Known Amino Acids New Natural Amino Acids New Amino Acids from Hydrolysates 4 Chemical Synthesis and Resolution of Amino Acids General Methods of Synthesis of a-Amino Acids Asymmetric Synthesis of a-Amino Acids Synthesis of Protein Amino Acids and Other Naturally Occurring a-Amino Acids a-Alkyl Analogues of Protein Amino Acids Synthesis of C-Alkyl and Substituted C-Alkyl a-Amino Acids Prebiotic Synthesis Models for Amino Acids a-Alkoxy a-Amino Acids and Related a-Heteroatom Substituted a-Amino Acids a-(Halogenoalkyl) a-Amino Acids Synthesis of Aliphatic a-Amino Acids Carrying Side-chain Hydroxy Groups Synthesis of Aliphatic a-Amino Acids Carrying Unsaturated Side-chains Synthesis of a-Amino Acids Carrying Aromatic and Heteroaromatic Side-chains Synthesis of N-Substituted a-Amino Acids Synthesis of a-Amino Acids Carrying Phosphorus-containing Side-chains Synthesis of a-Amino Acids Carrying Boron-containing Side-chains Synthesis of Labelled a-Amino Acids Synthesis of P- and Higher Homologous Amino Acids Laboratory Resolution of DL-Amino Acids Models for Prebiotic Enantioselection Relating to a-Amino Acids 5 Physico-chemical Studies of Amino Acids X-Ray Crystal Structures Nuclear Magnetic Resonance Spectromet ry Optical Rotatory Dispersion and Circular Dichroism Mass Spectrometry Other Spectroscopic and Related Studies Physico-chemical Studies Molecular Orbital Calculations 6 Chemical Studies of Amino Acids Racemization General Reactions of Amino Acids Specific Reactions of Amino Acids Effects of Electromagnetic Radiation on Amino Acids 7 Analytical Methods General Gas-Liquid Chromatography Ion-exchange and Related Forms of Chromatography Thin-layer Chromatography High Performance Liquid Chromatography Other Analytical Methods Assay of Specific Amino Acids Chapter 2 Peptide Synthesis By D. T. EImore 1 Introduction 2 Methods Amino-group Protection Carboxyl-group Protection Side-chain Protection General Deprotection Peptide Bond Formation Disulphide Bond Formation Solid-phase Peptide Synthesis Enzyme-mediated synthesis and Semi-synthesis Miscellaneous Reactions Related to Peptide Synthesis 3 Selected Examples of Peptide Synthesis 4 Appendix. A List of Synthesis Reported in 1991 Natural Peptides, Proteins, and Partial Sequences Sequential Oligo- and Poly-peptides Enzyme Substrates and Inhibitors Conformation of Synthetic peptides Glycopeptides Phosphopeptides Immunogenic Peptides Miscellaneous Peptides 5 Purification Methods References Chapter 3 Analogue and Conformational Studies on Peptide Hormones and other Biologically Active Peptides BY C. M. Blado?? 1 Introduction 3 Peptide-backbone Modifications yl [CSNHI-Analogues W [NHCOI-Retro-Inverso Analogues yl [CH2NH]-Amino Methylene Analogues Contents [CHXHI- and y, [CF--tH]-Ethylenic Isosteres Phosphono-Pept ides y, [CH20]-Methyleneoxy Analogues Miscellaneous Modifications C'-Terminal Modifications U,a -Dialkylated Glycine Analogues 3 Conformationally Restricted Cyclic and Bridged Analogues Rings and Bridges formed via Amide Bonds Bridges formed by Disulfide Bonds Miscellaneous Bridges and P-Turn Mimetics 4 Dehydroamino Acid Analogues 5 Enzyme Inhibitors Angiotensin Converting Enzyme (ACE) Inhibitors Renin Inhibitors HIV- 1 Protease Inhibitors Inhibitors of Other Proteases 6 Side-chain Interactions Studied by Residue Substitution or Deletion and Similar Modifications Peptides with 'Opioid Characteristics' Cholecystokinin Analogues Angiotensin and Analogues Oxytocin and Vasopressin Analogues Luteinising Hormone-releasing Hormone (LHRH) Analogues Substance P and Analogues Thyrotropin-releasing Hormone (TRH) Analogues Somatostatin Analogues Bradykinin Analogues Glucagon/Gastrin-releasing Peptides Miscellaneous Examples 7 Conformational Information derived from Physical Methods References Chapter 4 Cyclic, Modified, and Conjugated Peptides By J. S. Davies l Introduction 2 Cyclic Peptides General Considerations Naturally Occurring Dioxopiperazines (Cyclic Dipeptides) Other Dioxopiperazines Cyclotripeptides and Cyclotetrapeptides Cyclopentapeptides Cyclohexapeptides Cyclohepta and Cyclo-octapeptides Cyclononapeptides Cyclodecapeptides Higher Cyclic Peptides Peptides containing Thiazole Type Rings Cyclodepsipeptides Cyclic peptides containing Other Non-protein Ring Components 3 Modified Linear Peptides Phosphonopeptides 4 Conjugate Peptides G1 ycopeptide Antibiotics Other Glycopeptides Oligonucleotide Peptide Conjugates Lipopeptides and Related Conjugates 5 Miscellaneous Examples Chapter 5 P-Lactam Antibiotic Chemistry By C. H. Frydrych xii Contents 1 Introduction 245 2 New Natural Products 3 Biosynthesis 4 Penicillins and Cephalosporins 5 Clavulanic Acid and Oxapenams 6 Penems 7 Carbapenems, Carbacephems, and Related Systems 8 Azetidinones Reactions in which One Bond is Formed 1-2 Bond-forming Reactions 3 4B ond-forming Reactions 1-4 Bond-forming Reactions 2-3 Bond-forming Reactions Reactions in which Two Bonds are Formed + [3 l] Additions - 1-2 and 2-3 Bond Formation + [2 21 - Additions 1-2 and 3-4 Bond Formation 1 4a nd 2-3 Bond Formation Chemistry and Azetidinones Further Uses of Azetidinones 9 Major Structural Variants 10 Mechanistic Studies, Mode of Action, and Degradation Appendix: P-Lactam Antibiotics Prepared for Structure-activity Relationships and Miscellaneous P-Lactams References