Genomes, molecular biology and drug discovery:
Gespeichert in:
| Format: | Buch |
|---|---|
| Sprache: | English |
| Veröffentlicht: |
London [u.a.]
Acad. Press
1996
|
| Schlagworte: | |
| Online-Zugang: | Inhaltsverzeichnis |
| Beschreibung: | XII, 196 S. Ill., graph. Darst. |
| ISBN: | 0121377903 |
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| 245 | 1 | 0 | |a Genomes, molecular biology and drug discovery |c ed. by M. J. Browne ... |
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Datensatz im Suchindex
| _version_ | 1804125813429239808 |
|---|---|
| adam_text | jGenomes, Molecular Biology
and Drug Discovery
Edited by
M J BROWNE
SmithKline Beecham Pharmaceuticals
New Frontiers Science Park
Harlow, Essex
and
P L THURLBY
SmithKline Beecham Pharmaceuticals
New Frontiers Science Park
Harlow, Essex
ACADEMIC PRESS
Harcourt Brace amp; Company, Publishers
London San Diego New York
Boston Sydney Tokyo Toronto
Contents
Contributors ix
Introduction xi
I GENOME PROJECTS
1 The Human Genome Project: What We Want and What We Get 3
P Little
Abstract 3
1 The genome project 4
2 DNAsequencing 8
3 Alternative approaches 9
4 The example of chromosome 11 9
5 Unclonable DNAs 10
6 Computer data 11
7 Conclusion 11
Acknowledgements 12
References 12
2 Progress Towards a Complete Set of Human Genes 15
M D Adams
Abstract 15
1 Introduction 16
2 EST sequencing at The Institute for Genomic Research 16
3 Comparative gene anatomy 20
4 An expression map of the human genome 21
5 Using ESTs in tomorrow s research 23
6 The Institute for Genomic Research Database 24
References 24
3 The Mouse Genome 27
J -L Guenet
Abstract 27
1 Introduction 28
vi Contents
2 The mouse genome 29
3 Mapping the mouse genome 30
4 Markers used for the construction of genetic (linkage) maps 34
5 Strategies for the establishment of genetic (linkage) maps 38
6 Wild mice as a source of polymorphisms 40
7 Analysing the results of linkage experiments 42
8 The large-scale mapping programmes 43
9 Applications of the mouse genetic maps 44
10 Databases 48
Acknowledgements 49
References 49
H INTERPRETING THE CODE
4 Exploring the Vast Territory of Uncharted ESTs 55
J -M Claverie
Abstract 55
1 Introduction 56
2 The fraction of unknowns in genomic and partial cDNA sequences 57
3 Looking for new protein families in the set of unknown ESTs 60
4 Discussion 68
Acknowledgements 69
References 70
5 Prediction of Protein Structures and their Docking 73
P A Bates, R M Jackson and MJE Sternberg
Abstract 73
1 Introduction 74
2 Model building by homology 74
3 Protein fold recognition 77
4 Protein docking 79
5 Conclusion 85
References 85
HI FROM GENE TO TARGET
6 Expressing the Unknown: Considerations in Heterologous
Expression of Novel Gene Products to Optimize Determination
of their Functions 89
A R Shatzman
Abstract 89
1 Introduction 90
2 What s in a name? 92
3 Glutathione-S-transferase fusion proteins 98
Contents - vii
^ 4 Thioredoxin fusion proteins 99
j • 5 Cleavage of fusion proteins 99
6 Heterologous gene expression in insect cells 101
7 Heterologous gene expression in Drosophila 103
8 Concluding remarks 105
References 105
7 The GABAA Receptor Gene Family as Targets for Drug Discovery 107
P J Whiting, K L Hadingham, P B Wingrove, E Garrett, K Quirk,
K A Wafford, C I RaganandR M McKernan
Abstract 107
1 Introduction to the GABAA receptor 108
2 The GABAA receptor gene family 109
3 The composition of GABAA receptors in vivo 110
4 Expression and characterization of recombinant human GABAA receptors 112
5 Identification of novel drug binding sites 114
6 Determination of the function of GABAA receptor subtypes 114
7 Conclusions 115
References 115
8 Drug Discovery and the Transcriptional Control of the Human
Beta Globin Gene Locus 117
F Grosveld, M Antoniou, M Berry, E de Boer, N Dillon, D Drabek,
J Ellis, P Fraser, J Haley, S Philipsen, S Pruzina, S Raguz-Bolognesi,
D Smith,T Trimborn andM Wijgerde
Abstract 117
1 Introduction 118
2 Vectors for gene therapy 120
3 Transcription modulation as a basis for drug discovery for the
haemoglobinopathies 122
4 Screening model 125
Acknowledgements 126
References 126
IV FROM TARGET TO THERAPY
9 Drug Discovery and Optimization using Binary-Encoded Small
Molecule Combinatorial Libraries 131
J C Chabala, J J Baldwin, J J Burbaum, D Chelsky, L W Dillard,
I Henderson, G Li, MHJ Ohlmeyer, T L Randle, J C Reader,
L Rokosz and N H Sigal
Abstract 131
1 Introduction 132
2 Overview of binary-encoded combinatorial library synthesis 134
3 Combinatorial library synthesis and structure encoding 139
4 Lead discovery and optimization 146
viii Contents
Acknowledgements 149
References 149
10 Monoclonal Antibodies: Tools for Exploiting Gene Discovery 151
D P Bloxham
Abstract 151
1 Introduction 151
2 Principles of target selection 152
3 Properties of antibodies which can be exploited for therapeutic purposes 153
4 Genetic engineering has revolutionized the potential for antibody
use in vivo 154
5 Specific problems associated with antibody use 155
6 Septic shock 157
7 Rheumatoid arthritis 159
8 Asthma 161
9 Conclusions 162
Acknowledgements 163
References 163
11 Retroviral Vectors: First-Generation Systems for Gene Therapy 165
D E Onions
Abstract 165
1 Introduction 166
2 The retroviral life cycle and basis of vector systems 167
3 The safety of retroviral vectors 168
4 Future developments : 173
5 Conclusion 176
References 176
Appendix: Abstracts of Posters 179
Index 191
A colour plate section can be found between pages 84 and 85
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| title | Genomes, molecular biology and drug discovery |
| title_auth | Genomes, molecular biology and drug discovery |
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