Table Of ContentA Specialist Periodical Report
Amino-acids, Peptides, and
Proteins
Volume 2
A Review of the Literature Published
during 1969
Senior Reporter
G. T. Young, The Dyson Perrins Laboratory, University
of Oxford
SBN :8 5186 014 1
@ Copyright 1970
The Chemical Society
Burlington House, London, WIV OBN
Reporters
R. Elagrove, University of Oxford
C. C. F. Blake, Universify of Oxford
J. R. Brocklehurst, Uniuersity of Oxford
B. W. Bycroft, University of Notfingham
D. 6. Dalgleish, University of Oxford
J. S. Davies, University College of Swansea, University of Wales
R. Henson, University of Oxford
J. H. Jones, Universify of Oxford
P. H. Lloyd, University of Oxford
A. R. Peacocke, Universify of Oxford
R. N. Perham, Cambridge University
N. C. Price, University of Oxford
R. M. Stephens, Portsmouth Polyfechnic
1. 0. Walker, Universify of Oxford
Orgarric jormulne cornposed by Urfight’s, Syt?zbol\ct Method
PKINIkI> IN GKEAr BRITAIN BY JOHN WRIGHT AND SONS LTU., AT THL SlONEBRIDGE PRESS, BRISTOL
Preface
The scope of this Report, as for Volume 1, is essentially the chemistry of
amino-acids, peptides, and proteins, and the intention has been to review
all the relevant papers listed in Current Chemical Papers during 1969,
together with any appearing in the main journals that year even if not so listed.
It was, however, considered that the extent of the new work on metal
derivatives did not justify a separate chapter this year, and the papers
appearing in 1969 and 1970 will be reviewed together in the next Report.
Volume 1 contained a discussion of selected aspects of the relationship
between the structure and biological activity of peptides and proteins.
Systematic complete coverage of the literature in this field would constitute
a major extension of the scope of this Report; this has not been attempted
and no separate section has been included this year. On the other hand,
biological aspects have naturally been discussed in connection with the
chemistry in many parts of this volume. Comment should also be made on
the change in the title of Chapter 4. The term ‘peptides of abnormal
structure’ has been used in the past for peptides having structural features
(e.g. ester linkages) other than those typical of proteins. but of course such
peptides are by no means uncommon in Nature. In order to avoid possible
misinterpretation we have changed this year to the more cumbersome but
more accurate title ‘Peptides with Structural Features Not Typical of
Proteins’. This chapter now includes work on the penicillins and cephalo-
sporins. We shall be grateful if our attention is drawn to any important
omissions in the bibliography, in order that the references may be included
in the next volume.
As in Volume 1, there is an author index but not a subject index, and the
extended list of contents will, we hope, assist the reader in finding the
section he requires. Reference numbers apply to the chapter in which they
occur or, if the chapter is divided into parts, to the part concerned. For
the convenience of readers, we have reprinted as Chapter 5 the main
.
recommendat ions of the I.U .P.A .C .-I. U.B Commission on Biochemical
Nomenclature relevant to this field.
I would again thank warmly the contributors who have made my
editorial task so pleasant.
G. T. YOUNG
Cont en ts
Chapter 1 Amino-acids
By 5. W. Bycroft
1 Naturally Occurring Amino-acids 1
A Introduction 1
B New Free Occurring Amino-acids 1
C New Amino-acids from Peptide Hydrolysates 2
D Occurrence of Known Amino-acids 4
2 Chemical Synthesis and Resolution of Amino-acids 4
A Introduction 4
B Protein Amino-acids 4
C Other Naturally Occurring Amino-acids 4
D a-Alkyl-a-amino-acids 5
E a-Dialkyl-a-amino-acids 7
F a-Amino-acids with Aliphatic Hydroxy-groups in
the Side-chain 8
G N-Subst i t uted-a-amino-acids 8
H a-Amino-acids Containing Sulphur or Selenium 9
I A List of a-Amino-acids which have been Syn-
thesised for the First Time 10
J Labelled Amino-acids 11
3 Physical and Stereochemical Studies of Amino-acids 12
A Determination of Absolute Configuration 12
B Crystal Structures of Amino-acids 14
C Optical Rotatory Dispersion (0.r.d.) and Circular
Dichroism (C.d.) 14
D Nuclear Magnetic Resonance (N.m.r.) Spectra 15
E Mass Spectrometry 16
4 Chemical Studies of Amino-acids 16
A General Reactions 16
B Other Reactions 18
C Non-enzymic Models of Biochemical Processes
Involving Amino-acids 19
D Effects of Electromagnetic Radiation on Amino-
acids 21
5 Analytical Methods 22
A Ion-exchange Chromatography 23
B Thin-Layer chromatography 23
C Other Methods 23
D Determination of Specific Amino-acids 23
vi Contents
Chapter 2 Structural Investigation of Peptides and Proteins
1 Primary Structures and Chemical Modification
By R. N. Perham
1 Introduction 25
2 Methods 25
A Amino-acid Analysis 25
Ion-exchange Chromatography 26
High-voltage Electrophoresis and Thin-layer
Chromatography 28
Gas-Liquid Chromatography 28
B End-group Analysis 29
C Sequential Degradation and Mass Spectrometry 31
D Peptide Chain Cleavage 34
Proteolytic Enzymes 34
E Fractionation Methods 36
3 Structural Proteins 39
A The Crystallins 39
B Muscle Proteins 40
C Collagen 40
Primary Structure 40
Cross-links 42
D Elastin 44
E Chromosomal Proteins 45
F Miscellaneous 47
Serum and Egg Proteins 47
Wool and Others 47
4 Peptides and Hormones 49
A Growth Hormone 49
B Insulin 49
C Interstitial-cell Stimulating Hormone (ICSH) 50
D Other Hormones 50
E Peptides 51
5 Enzymes 52
A Proteolytic Enzymes 52
B Other Enzymes 55
C Haemoglobin, Myoglobin, and Cytochroines 59
D Studies on Quaternary Structure 63
6 Immunoglobulins 63
A Light Chains 63
B Heavy Chains 64
C Antibody Binding Sites 65
Conterz ts vii
7 Chemical Modilkation of Proteins 67
A Tryptophan, Tyrosine, and Histidine Residues 67
R Cysteine Residues and Disulphide Bridges 69
C Amino-groups 71
D Carboxy-groups 72
I/ X-Ray Studies
By C. C. F. Blake
1 Amino-acids and Oligopeptides 73
A DL-Proline 73
B DL-Valine 73
C Dipeptides 73
D Glycylprolyl-IeucylgIycine 75
2 Folypeptides 75
3 Globular Proteins 77
A Methods 77
Isoinorphous Derivatives 77
Direct Methods 79
Diffraction Techniques 80
B Results 81
Insulin 81
Car boxypeptidase 83
Subtilisin 86
Chymotrypsin 88
Staphylococcal Nuclease 90
Lactate Dehydrogenase 91
Haem Proteins 93
Preliminary Data for Other Proteins 94
Ill Spectroscopic and Solution Studies on the Conf ormation
and Interactions of Polypeptides and Proteins
By A. R. Peacocke
1 Introduction 96
2 Infrared 97
Contributed by R. M. Sfephens
3 Optical Rotatory Dispersion and Circular Dichroism 100
Contributed by D. G. Dalgleish
A General 100
H Amino-acids and Sniall Model Compounds 102
C Polypeptides 104
D Metal Ion Complexes 106
...
Contents
Vlll
E Haem Proteins 107
F Binding of Other Molecules to Proteins 109
G Aggregation, Disaggregation, and Denaturation 111
H Lipoproteins and Membranes 113
I Native and Modified Proteins 114
4 Nuclear Magnetic Resonance 117
Confribufed by R. Henson
5 Fluorescence 123
Contributed by J. R. Brocklehursf
6 Spin Labels 127
Contribufed by N. C. Price
A Measurements of Correlation Time 128
B Interaction of the Unpaired Electron with Neigh-
bouring Paramagnetic Ions or Nuclei 131
C Interaction of the Unpaired Electrons in a Bi-
radical 132
7 Dissociation and Association of Proteins 133
Contributed by R. Blagrove, P. H. Lloyd, and I. 0. Walker
A Dissociating Agents 133
B Equilibrium Studies 136
C Dynamic Studies 139
8 Diffusion 141
Contributed by R. Blagrove
Chapter 3 Peptide Synthesis
By J. H. Jones
1 Introduction 143
2 Methods 144
A Protective Groups 146
Protection of Amino-groups 146
Protection of Carboxy-groups 150
Protection of Histidine Side-chains 152
Protection of Thiol Groups 153
B Formation of the Peptide Bond 154
Activated Esters 154
Other Methods 156
Racemisat ion 158
C Repetitive Methods of Peptide Synthesis 159
Solid-phase Synthesis 159
Other Repetitive Methods 164
D Synthesis of Homodetic Cyclic Peptides 165
Contents ix
E Synthesis of Polymeric Models for Studies in Pro-
tein Chemistry 167
Polyamino-acids 167
Sequential Polypeptides 169
3 Syntheses Achieved 172
A Cytochrome c 172
B Proinsulin 174
C Ribonuclease T, 175
D Staphylococcal Nuclease 177
4 Appendix A: A List of Syntheses reported in 1969 180
A Natural Acyclic Peptides, Peptide Hormones,
Proteins, Analogues, and Partial Sequences I80
B Homodetic Cyclic Peptides 184
C Sequential Polypeptides 185
D Miscellaneous Peptides 186
5 Appendix B: A List of Some Useful New Synthetic Inter-
mediates which were described during 1969 188
Chapter 4 Peptides with Structural Features Not Typical of
Proteins
By J. S. Davies
1 Introduction 192
2 Biosynthesis of Peptide Antibiotics and Microbial
Peptides 192
3 Cyclic Peptides 194
A 2,5-Dioxopiperazines 195
B Gramicidins 196
C Circulin B 198
D Polymyxins 198
E Viomycin 198
F Peptides of Amanita phalloides 199
G Tyrocidins 200
H Other Cyclic Peptides 200
4 Depsipeptides 200
A Valinomycin 200
B Enniatins 202
C Esperin 203
D Stendomycin 203
E Beauvericin 204
F Actinomycins 204
G Synthesis 205
H Quinoxaline Antibiotics 206
I Miscellaneous 206
X Contents
5 Peptide-Carbohydrate Linkages 208
A Glycopeptides 208
B Amino-acid-Carbohydrate Antibiotics 214
6 Peptides and Amino-acids Linked to Nucleosides and
Nucleotides 214
A Peptidyl-tRNA 214
B Nucleopeptides 21 5
C Polyoxins 21 7
7 Peptide Alkaloids 217
8 Peptides and Amino-acids Conjugated to Lipids 218
9 Penicillins 21 9
10 Cephalosporins 22 1
11 Feptide Analogues 223
12 Miscellaneous 223
Chapter 5 Extracts from the Tentative Rules of the 1.U.P.A.C.-
I.U.B. Commission on Biochemical Nomenclature
I Tentative Abbreviated Designation of Amino-acid Deri-
vatives and Peptides
1 General Considerations 226
2 Abbreviations for Amino-acids 227
3 Amino-acid Residues 228
4 Substituted Amino-acids 230
5 Bolypeptides 23 1
6 Abbreviations for Substituents 233
II Tentative Rules for Naming Synthetic Modifications of
Natural Peptides
Introduction 234
Rules 234
Summary with Examples 23 8
Ill Tenf af ive Abbreviated Nomen cldure of Synthetic Poly-
peptides (Polymerised Amino-acids)
Definitions 239
Rules 240
Examples 24 1
