Amino Acids, Peptides and Proteins (SPR Amino Acids, Peptides, and Proteins (RSC)) (Vol 1)

321 Pages·1969·20.25 MB·English

by  J. H. Jones

A Specialist Periodical Report
Amino-acids, Peptides, and
Proteins
Volume 1
A Review of the Literature Published
during 1968
Senior Reporter
G. T. Young, The Dyson Perrins Laboratory, University of Oxford
Reporters
C. C. F. Blake, University of Oxford
J. S. Davies, Universify College of Swansea, University of Wales
R. D. Gillard, University of Kent
P. M. Hardy, Universify of Exefer
J. H. Jones, Universify of Oxford
S. Laurie, Universify of Kent
R. N. Perharn, Cambridge University
D. G. Srnyth, Nafional Institute for Medical Research, London
SBN: 85186 004 4
@ Copyright 1969
The Chemical Society
Burlington House, London, WIV OBN
The introduction of Specialist Periodical Reports, giving comprehensive
accounts of progress in specialised, limited areas of chemistry, is an
important development in the publications policy of the Chemical Society.
These volumes are designed to assist the research worker in his own field,
and their appearance allows the long-established AnnuaZ Reports on the
Progress of Chemistry to return to their original aim, to keep the non-
specialist informed of the highly significant advances in the major fields of
pure chemistry.
I was asked by the Reports and Reviews Committee of the Society to
invite experts to collaborate in the production of a Report on Amino-acids,
Peptides, and Proteins. It seemed to me that it would be unreasonable to
ask active workers to extend their survey much beyond the area of their
special interest, and this volume is therefore the result of the co-operation
of eight authors. I must make it clear that my contribution goes no further
than the overall editorial supervision, and I record here my gratitude to
each author for his willing help. I believe that those working or intending
to work in this field will be grateful also.
The scope of the Report is essentially limited to the chemistry of amino-
acids, peptides, and proteins, but Chapter 5 discusses some aspects of the
relationship between the structure and biological activity of selected
peptides and proteins; the Annual Reports for 1968 include a section on
Enzyme Mechanisms. The intention has been to review all relevant papers
listed in Current Chemical Papers during 1968, together with those appear-
ing in the main journals that year even if not so listed, but the late arrival in
this country of some December issues of U.S. journals prevented their
inclusion in this survey. Some papers published early in 1969 have been
noted. The delay which would be involved in forming a subject index was
considered to be unacceptable, and it is hoped that the extended list of
contents will enable readers to find material without difficulty; an Author
Index is included. It should be noted that reference numbers apply to the
Chapter in which they occur, or, if the Chapter is divided into Parts, to the
Part concerned.
We have adopted the abbreviated designations of amino-acid derivatives
and polypeptides recommended in I.U .P.A.C . Information BuZZetin No. 25
(1966). There are still examples in the literature of formulations, parti-
cularly of branched-chain and cyclic polypeptides and depsipeptides,
which are ambiguous because these Rules are not followed; for
iv Preface
example, Glu must be understood to mean 0-(y-glutamy1)-threonine, and
I
Thr
N-(a-glutamy1)-threonine is formulated as Glu-Thr. Rearrangement of
structures to give the correct alignment may at times be awkward, but an
ambiguous formulation is still more undesirable, and we appeal to authors
and editors to adopt the conventions which have been agreed internation-
ally.
In a survey of this kind, overlap between sections is bound to occur and,
within limits, is desirable, for the convenience of the reader. It was felt
that it would be helpful in certain sections to give in this first issue a brief
introductory account of earlier work; this will not of course be appropriate
in subsequent years. It is intended that these Reports should appear
annually, and the second volume will survey literature published in 1969,
together with any important papers which escaped our search this time; we
shall be grateful if our attention is drawn to such omissions. Authors can
assist us here, as well as themselves, by ensuring that the titles of their
papers indicate the contents as clearly as possible. Some modification of
treatment will be made in the next volume, and we shall welcome comments
and criticisms, but we hope that the reader will find the arrangement of the
material convenient on the whole.
Among the important advances recorded in this volume are the three-
dimensional structure of yet another enzyme, papain, the complete amino-
acid sequence of several other enzymes, and the chemical synthesis of
material having the enzymic activity of ribonuclease. The increasing rate
of progress is likely to make future volumes still more difficult to confine
within a reasonable size, but one could hardly ask for a more exciting time
at which to review the field.
G. T. YOUNG
Contents
Chapter 1 Amino-acids
By J. H. Jones
1 Naturally Occurring Amino-acids
A Occurrence of Known Amino-acids
B New Naturally Occurring Amino-acids
C A List of New Naturally Occurring Amino-acids
2 Chemical Synthesis and Resolution of Amino-acids
A Protein Amino-acids
B Other a-Amino-acids
C a-Dialkyl-a-amino-acids
D Amino-acids with Aliphatic Hydroxyl Groups in
the Side-chain 7
E N-Substituted Amino-acids 9
F P-Amino-acids 11
G Labelled Amino-acids 11
H A List of a-Amino-acids which have been Syn-
thesised for the First Time 13
3 Physical and Stereochemical Studies of Amino-acids 15
A Determination of Absolute Configuration 15
B Crystal Structures of Amino-acids 16
C Optical Rotatory Dispersion and Circular
Dichroism 17
D Nuclear Magnetic Resonance Spectra 17
4 Chemical Studies of Amino-acids 19
A General Reactions 19
B Other Reactions 20
C Non-enzymic Models of Biochemical Processes
Involving Amino-acids 22
D Effects of Electromagnetic Radiation on Amino-
acids 23
vi Cont ents
5 Analytical Methods 26
A Gas-Liquid Chromatography 26
B Ion-exchange Chroma tograph y 27
C Thin-layer Chromatography 28
D Other Methods 29
E Determination of Specific Amino-acids 30
Chapter 2 Structural Investigation of Peptides and Proteins
I Primary Structures and Chemical Modification
By R. N. Perham
1 Introduction 31
2 The Methodology of Amino-acid Sequence Determination 32
A Amino-acid Analysis 32
Ion-exchange Chromatography 33
High-voltage Paper Electrophoresis and Thin-layer
Chromatography 34
Special Techniques for Tryptophan 34
Gas-Liquid Chromatography 36
B End-group Analysis 38
N-Terminal Methods 38
C-Terminal Methods 41
C Sequential Degradation 42
The Edman Method 42
Other Chemical Methods 43
D Blocked End-groups 44
E Amino-acid Sequence by Mass Spectrometry 45
Fragmentation of Peptide Derivatives 46
Techniques for Sequence Determination 47
Use of Computers for Sequence Determination 50
Prospects 50
F Peptide Chain Cleavage and Peptide Fractionation 51
Proteolytic Enzymes 51
Chemical Methods of Chain Cleavage 52
Chemical Modification and Enzymic Cleavage 55
(i) Modifications of lysine 55
(ii) Modifications of arginine 58
(iii) Use of aminoethylation 58
Peptide Fractionation 59
G Diagonal Paper Electrophoresis 61
General Principles 61
Diagonal Method for Cystine Peptides 62
Contents vi i
Lysine Diagonals 63
Diagonal Methods for Cysteine Residues 64
Other Diagonals 66
H General Conclusions 67
3 Structural Proteins 68
A The Structural Proteins of Muscle 68
Actin 69
Myosin 70
B Collagen 71
The Primary Structure of Collagen 72
The Nature of the Collagen Cross-links 73
Some Comparisons with Other Structural Proteins 76
C Fibrinogen 77
D The Histones 79
4 Peptides and Hormones 82
A Growth Hormones 82
B Insulin 83
C Calcitonin 85
D Gastrin and Caerulein 86
E Venom Peptides 86
5 Enzymes 87
A Proteolytic Enzymes 87
Serine Proteinases 87
0t her Proteinases 93
B Other Enzymes 95
C Haem Proteins 100
Haenioglobin and Myoglobin 100
Cytochromes 102
D Studies on Quaternary Structure 104
6 Immunoglobulins 104
A Light Chains 105
B Heavy Chains 105
C Disulphide Bridges 106
D Haptoglobin and Haemagglutinin 107
7 Chemical Modifications of Proteins 108
A Reactions of Lysine and Arginine 108
€3 Reactions of Carboxyl Groups 109
C Reactions of Cysteine and Cystine 110
D Cross-linking Reactions 110
viii Contents
/I Secondary Structures
By P. M. Hardy
1 Introduction 112
2 Infrared 114
3 Optical Rotatory Dispersion and Circular Dichroism 115
4 Nuclear Magnetic Resonance 120
5 Hydrogen Exchange 123
6 Conformational Probes 124
7 Theoretical Approaches to Peptide Conformations 127
8 The Conformations of Small Peptides 130
9 Cyclic Peptides 132
10 Polyamino-acids: Studies in Non-aqueous Solution 137
11 Polyamino-acids: Studies in Aqueous Solution 139
12 Copolymers 142
13 Sequential Polypeptides 143
14 The Helix-Coil Transition 145
15 Some Conformational Aspects of Proteins 148
16 Recent Applications of Physical Methods to the Study of
Protein Conformations 150
Ill X-Ray Analysis
By C. C.F . Blake
1 Oligopeptides: Glycylglycine (a-Form) 154
2 Globular Proteins 154
A Methods 154
B Results 157
Chymotrypsin 157
Haemoglobin 163
Papain 169
Aspartate Transcarbamylase 170
Human Immunoglobulin G 172
3 Fibrous Proteins: Muscle 172
Contents ix
Chapter 3 Peptide Synthesis
By J. H. Jones
1 Introduction 174
2 Methods 175
A Protective Groups 175
Protection of Amino-groups 175
Protection of Carboxyl Groups 179
Protection of Side-chain Functional Groups 181
Protection of Thiol Groups and the Synthesis of
Cysteine Peptides 184
B Formation of the Peptide Bond 187
Activated Esters 187
Other Methods 189
Racemisat ion 192
C Repetitive Methods of Peptide Synthesis 193
Synthesis on a Polymeric Support 193
The Use of N-Carboxy-anhydrides 196
0t her Methods 197
D Synthesis of Cyclic Peptides 198
E Synthesis of Polymeric Models for Studies in
Protein Chemistry 199
Polyamino-acids 199
Sequential Polypeptides 200
3 Syntheses Achieved 201
A Bovine Pancreatic Ribonuclease 201
B Apoferredoxin 203
C Glucagon 203
D Secretin 205
E Gastrins 205
F Thyrocalcitonin 205
4 Appendix: List of Syntheses Reported in 1968 205
A Natural Acyclic Peptides, including Analogues
and Partial Sequences 205
B Cyclic Peptides 208
C Sequential Polypeptides 209
D Miscellaneous Peptides 209