Amino Acids and Peptides (SPR Amino Acids, Peptides (RSC))vol.19

348 Pages·1988·18.3 MB·English

by  J. H. Jones

Amino Acids and Peptides
Volume 19

A Specialist Periodical Report
Amino Acids and Peptides
Volume1 9
A Review of the Literature Published
during 1986
Senior Reporter
J. H. Jones, University of Oxford
Reporters
G. C. Barrett, Oxford Polytechnic
J. S. Davies, University College of Swansea
I. J. Galpin, University of Liverpool
P. M. Hardy, University of Exeter
R. W. Hay, University of Stirling
K. B. Nolan, University of Surrey
A. V. Stachulski, Beecham Pharmaceuticals
SOCIETY OF
MISTRY
ISBN 0-85 186- 174- 1
ISSN 0269-752 1
0 The Royal Society of Chemistry, 1987
All Rights Reserved
No purr of this book may be reproduced or transrnirted in an! form
or by any means - graphic, electronic, including photocopying, recording,
taping, or information storage arid retrieval system - without
written permission froin Re Royal Society of Chemisrn
Published by The Royal Society of Chemistry
Burlington House, Piccadilly, London W 1V OBN
Printed in England by Staples Printers Rochester Limited,
Love Lane, Rochester, Kent.
Preface
We have not been made aware of any major general works on the
chemistry of amino acids and peptides, although there has of
course been the usual crop of specialist monographs' and symposium
proceedings. On the other hand, there have been two noteworthy
texts covering the pharmacological background which provides
the principal justification and motivation for a large part
of the chemical effort surveyed in these Specialist Periodical
Reports. In their 'Principles of Endocrine Pharmacology', Thomas
2
and Keenan give clear and up-to-date (at mid-1985) accounts
of the functions and pharmacology of hypothalamic hormones,
the anterior pituitary hormones, the posterior pituitary hormones,
parathyroid hormone , calcitonin , and insulin. The €ift h edition'
of a well-known introduction to neuropharmacology is also
commended: it has a most stimulating discussion of the neuroactive
peptides. This is an area of great complexity, which increases
relentlessly with the discovery of new peptide factors and
activities, and it will be a long time before all the pieces
of the puzzle fall into place. It is already clear that the
interpretation of the roles of the neuropeptides will lead towards
an understanding of the workings of the brain aild provide a
basis for the rational design of drugs €or use in neurological
and psychiatric disorders. Quite a lot can be said about what
the neuropeptides can do in experimental systems, but what are
they for in Nature? At first it was thought that they were
like the neurotransmitters of classical pharmacology. Now
they are generally regarded as modulators of neural activity
- a high sounding but imprecise phrase, like a politician's
answer to a tricky question. But there is room for speculation
and hypothesis at a fundamental level here, and it has been
argued (in a new journal which looks like one which should
be watched) that 'peptides are an overelaborated form of messenger
for engaging in the relatively simple informational events
associated with neurotransmission', and suggested that there
may be other functions, to do with nerve growth and development.
vi Amino Acids and Peptides
The advice with which Cooper, Bloom, and Roth3 conclude their
book is sound: 'Stay tuned, the data flow fast'.
Bal Ziol College, Oxford John Jones
July 1987
References
1. Note especially The Peptides, 1985, 1 (ed. V. J. Hruby, Academic Press,
New York, etc.: deals with the study of peptide conformations and
interactions, in relation to drug design, by c.d., fluorescence,
theoretical, and n.m.r. methods) and T. Wieland, 'Peptides of Poisonous
Amanita Mushrooms', Springer, New York, etc., 1986.
2. J. A. Thomas and E.J. Keenan, 'Principles of Endocrine Pharmocology',
Plenum Medical Book Company, New York and London, 1986.
3. J. R. Cooper, F. E. Bloom, and R. H. Roth, 'The Biochemical Basis of
Neuropharmacology', 5th Edn., Oxford University Press, New York and
Oxford, 1986.
4. J. S. Morley, Drug Design and Delivery, 1986, 1, 47. This new journal
is published by Harwood Academic Publishers GmbH.
Contents
Chapter 1 Amino Acids
By G. C. Barrett
1 Introduction
2 Textbooks and Reviews
3 Naturally Occurring Amino Acids
Occurrence of Known Amino Acids
Uncommon Amino Acids in Peptides and Proteins
New Natural Amino Acids
New Amino Acids from Hydrolysates
4 Chemical Synthesis and Resolution 4
General Methods of Synthesis of a-Amino Acids 4
Asymmetric Synthesis of @-Amino Acids 5
Synthesis of B- and Higher Homologous Amino
Acids 7
Prebiotic Synthesis Models for Amino Acids 8
Synthesis of Protein Amino Acids and Other
Naturally Occurring a-Amino Acids 8
Synthesis of a -Alkyl Analoques of Protein
Amino Acids 14
Synthesis of Other Aliphatic Amino Acids 14
Synthesis of Halogenoalkyl Amino Acids 15
Synthesis of Amino Acids with Unsaturated
Side Chains 15
Synthesis of Hydroxyalkyl Amino Acids 17
Synthesis of Amino Acids with Aromatic or
Heteroaromatic Side Chains 17
Synthesis of N-Substituted Amino Acids 18
Synthesis of Amino Acids containinq Sulphur
or Selenium 18
Amino Acids Synthesized for the First Time 18
Synthesis of Labelled Amino Acids 19
Resolution of DL-Amino Acids 20
5 Physical and Stereochemical Studies of Amino
Acids 23
Crystal Structures of Amino Acids and Their
De r i v at i ve s 23
Nuclear Magnetic Resonance Spectrometry 23
Optical Rotatory Dispersion and Circular
D i c hro i sm 24
Mass Spectrometry 25
Other Spectroscopic Studies 25
Other Physical Studies 26
Molecular Orbital Calculations 27
viii Amino Acids and Peptides
6 Chemical Studies of Amino Acids 27
Racem i za t i on 27
General Reactions of Amino Acids 28
Specific Reactions of Amino Acids 31
Non-enzymic Models of Biochemical
Processes Involving Amino Acids 33
Effects of Electromagnetic Radiation on
Amino Acids 33
7 Analytical Methods 35
Ga s- L i qu i d Chroma tog raph y 35
Ion-exchange Chromatography 35
Thin-layer Chromatography 36
High-performance Liquid Chromatography 36
Fluorescence Methods 39
Other Analytical Methods 39
Determination of Specific Amino Acids 39
References 40
Chapter 2 Peptide Synthesis
.
By I.J Galpin, with Appendices compiled
by C.M. Galpin
1 Introduction 58
2 Methods
Protective Groups 59
Es tab1 i shed Methods of Amino-group 59
Protection 59
New Methods of Amino-group Protection 62
Carboxyl Protection 65
Side-chain Protection 65
General Deprotection 71
Formation of Peptide Bonds 74
Racem i za t i on 78
Repetitive Methods of Peptide Synthesis 80
Enzyme-mediated Synthesis and Semi-synthesis 89
3 Synthesis 93
4 Appendix I: A List of Syntheses Reported in 1986 96
Natural Peptides, Proteins, and Partial
Sequences 96
Sequential Oligo- and Poly-peptides 107
Enzyme Substrates and Inhibitors 107
G1 ycopept ide s 110
Miscellaneous Peptides 110
5 Appendix 11: Amino Acid Derivatives Useful
in Synthesis 114
Coded Amino Acids 114
Uncoded Amino Acids 117
Contents ix
6 Appendix 111: Purification Methods 119
High-performance Liquid Chromatography 119
Gas-Liquid Chromatography 121
0 ther Chroma tograph i c Me thod s 121
References 122
Chapter 3 Analogue and Conformational studies on
Peptide Hormones and Other Biological~y
Active Peptides
By J.S. Davies
1 Introduction 141
2 Peptide-backbone Modifications 141
Y [CSNH]- Analogues 141
Y [NHCOI -Retro-Inverso Analogues 142
Y [CONR]- N-Alkylated Analogues 144
Y"CH2NHl-Amino Methylene Analogues 144
Y [CH=CH]- Ethylenic Isosteres 144
Y (COCH21-Keto Methylene Analogues 145
Y [CH2O]-Methyleneoxy Analogues 145
Y [CON(OH) 1 -N-Hydroxy Analogues 147
Y [CSC]- Acetylene Isostere 147
Y [CH=N+-O'l -Nitrono Isostere 147
Y [CHzS]- Thiomethylene Analogues 147
Phosphono-Peptides 147
Aza-Pept ides 148
Replacement of L- by D-Residues 148
CI ,a-Dialkylated Glycine Analogues 149
3 Conformationally Restricted Bridged Analogues 150
Soma tos ta t i n 150
En kephal ins 152
Substance P and Neurotensin Analogues 152
ACTH, Vasopressin, and Bradykinin Analogues 153
Other Cyclic Analogues 153
4 Dehydroamino Acid Analogues 155
5 Enzyme Inhibitors 156
Angiotensin Converting Enzyme (A.C.E.)
Inhibitors 156
Renin Inhibitors 158
Other Inhibitors 160
6 Side-chain Interactions Studied by Residue
Substitution or Deletion, and Related
Modifications 162
7 Conformational Information Derived from
Physical Methods 172
Nuclear Magnetic Resonance Techniques 172
X-Ray and Related Techniques 176
Infrared and Circular Dichroism Studies 177
Compu t at i onal Me t hod s 179
References 180