Peptides as drugs: discovery and development
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| Other Authors: | |
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| Format: | Book |
| Language: | English |
| Published: |
Weinheim
WILEY-VCH-Verl.
2009
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| Subjects: | |
| Online Access: | Inhaltstext Inhaltsverzeichnis |
| Item Description: | Literaturangaben |
| Physical Description: | XV, 226 S. Ill., graph. Darst. 25 cm |
| ISBN: | 9783527322053 |
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MARC
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Titel: Peptides as drugs
Autor: Groner, Bernd
Jahr: 2009
Contents
Prefacce %i
List of Contributors xiii
1 Peptides as Drugs: Discovery and Development 1
Bernd Qroner
1.1 Discovery of New Potential Drug Targets and the
Limitations of Druggability 1
1.2 Protein Interaction Domains Are at the Core of Signaling
Pathways 4
1.3 Peptides as Inhibitors of Protein Interactions 5
References 7
2 Mimics of Growth Factors and Cytokines 9
JQrgen Scheller, Joachim Crotzinger, and Stefan Rose-John
2.1 Introduction 9
2.2 The Cytokines 9
2.2.1 The Receptors 11
2.2.2 "Simple" Receptors 12
2.2.3 "Complex" Receptors 13
2.3 Defining Receptor Recognition Sites in Cytokines Using
Chimeric Proteins 35
2.4 Receptor Recognition Sites are Organized as Exchangeable
Modules 17
2.5 The Concept of Fusing the Cytokine to the Soluble Receptor:
Hyper-IL-6 19
2.6 Antagonists Specifically Inhibiting IL-6 Trans-Signaling 20
2.7 In Vitro Evolution of Peptides and Proteins 22
2.7.1 Platforms for the Selection of High-Affinity Binders 24
2.7.2 Agonists and Antagonists of Cytokines and Growth
Hormones 27
2.8 Concluding Remarks 28
References 29
3 Peptides Derived from Exon v6 of the CD44 Extracellular Domain
Prevent Activation of Receptor Tyrosine Kinase and
Subsequently Angiogenesis and Metastatic Spread
of Tumor Cells 35
Helmut Ponta and Veronique Orion-Rousseau
3.1 Introduction 35
3.2 CD44 Proteins and Their Involvement in RTK Activation 36
3.3 CD44v6 Acts as a Coreceptor for c-Met and Ron 37
3.4 Three Amino Acids in CD44 Exon v6 Are Crucial for the CD44v6
Coreceptor Function, and Small Peptides Can Interfere with This
Function 3$
3.5 The Ectodomain of CD44v6 Binds to HGF 42
3.6 Peptides Corresponding to Exon v6 of CD44 Inhibit Metastatic
Spread of Tumor Cells 43
3.7 The Significance of the Collaboration between CD44v6 and
c-Met In Vivo 45
3.8 The CD44v6 Peptides Interfere with Angiogenesis 46
3.9 Outlook 48
References 49
4 Peptide Aptamers Targeting the Viral E6 Oncoprotein Induce
Apoptosis in HPV-positive Cancer Cells 57
Felix Hoppe-Seykr, Susanne Dymalla, Markus A. Moosmeier, and
Karin Hoppe-Sey/er
4.1 Human Papillomaviruses and Oncogenesis 57
4.1.1 Cervical Cancer 58
4.1.2 The E6 and E7 Genes 59
4.2 Peptide Aptamers Targeting the HPV E6 Oncoprotein 62
4.3 E6-Targeting Peptide Aptamers: Therapeutic Perspectives 64
4.3.1 Therapeutic Target Protein Evaluation by Peptide Aptamers 64
4.3.2 The Intrinsic Therapeutic Potential of Peptide Aptamers 65
4.3.3 Identification of Functional Peptide Mimics by Displacement
Screening 67
4.4 Perspectives 68
References 69
5 The Prevention of HIV Infection with Viral Entry Inhibitors 73
Lisa Egerer, Anne Hubert, DorotheevonLaer, and Ursula Dietrich
5.1 Introduction: The Potential of Peptides as Drugs in the
Treatment of HIV Infection 73
5.2 The HIV Entry Process 75
5.3 Peptides that Inhibit Receptor or Coreceptor Binding 77
5.3.1 Physiological Antimicrobial Peptides 77
5.3.1.1 Defensins 77
5.3.2 Chemokines 78
5.3.3 Synthetic Peptides and Peptidomimetics 79
5.4 Inhibitors of the Viral and Cellular Membrane Fusion
Process 81
5.5 Entry Inhibitory Peptides Selected by the Phage Display
Technology 83
5.6 Limitations of Peptides in the Treatment of HIV Infection 84
5.7 Strategies to Prolong the In Vivo Half-Life of Antiviral
Peptides 85
5.8 Antiviral Peptides in Gene Therapy of HIV Infection 88
References 93
6 Intracellular Expression of Peptides 203
Christian Wichmann, Yvonne Becker, and Manuel Crez
6.1 Introduction 103
6.2 Peptide Design and Expression Cassettes 103
6.3 Stable Delivery and Expression of Peptides: Gamma-Retro- and
Lentiviral Vectors 106
6.4 Gamma-Retroviral Vectors 109
6.5 Lentiviral Peptide Delivery 111
6.6 Vectors for Transient Expression of Peptides: Adenoviruses and
Adeno-Associated Viruses 114
6.7 Perspective 119
Acknowledgments 120
References 120
7 The Internalization Mechanisms and Bioactivity of the
Cell-Penetrating Peptides 125
Mats Hansen, Elo Eriste, and Oh Langel
7.1 Introduction 125
7.2 Discovery and Classification of CPPs 125
7.3 Internalization Mechanisms of Cell-Penetrating
Peptides 126
7.4 Models of CPP Uptake 128
7.5 The Current View of CPP Uptake 129
7.6 CPPs as Cargo Delivery Vehicles 130
7.7 Delivery of Proteins 131
7.8 CPPs in Gene Delivery 131
7.9 Delivery of Oligonucleotides 131
7.10 Cytotoxicity of Cell-Penetrating Peptides 133
7.11 In Vivo Drug Delivery with CPPs 134
7.12 CPPs for Targeted Delivery 136
7.13 Conclusions 136
Acknowledgments 137
References 137
Abbreviations 137
I
g Production and Purification of Monomeric Recombinant Peptide
Aptamers: Requirements for Efficient Intracellular Uptake and
Target Inhibition 145
Corina Borghouts and Astrid Weiss
8.1 Introduction 145
8.2 Protein Production 146
8.2.1 Bacterial Systems 148
8.2.2 Yeast Systems 150
8.2.3 Baculovirus Systems 152
8.2.4 Chemical Synthesis 153
8.3 Protein Purification 154
8.3.1 Ammonium Sulfate Fractionation 154
8.3.2 Affinity Chromatography 155
8.3.3 Buffer Exchange and Desalting 156
8.3.4 Ion-Exchange Chromatography 156
8.3.5 Hydrophobic Interaction Chromatography 156
8.3.6 Size-Exclusion Chromatography 157
8.4 Isolation of Monomeric, Natively Folded Proteins 157
8.4.1 Correct Refolding versus Aggregation 157
8.4.2 Techniques for Protein Folding 158
8.4.3 Factors Influencing Refolding 159
8.5 Increasing Peptide Production, Purification and Efficacy by Using
Scaffolds 161
8.5.1 Properties and Requirements of Scaffolds 161
8.6 The Use of Cell-Penetrating Peptides for Cellular Uptake of Purified
Proteins 162
8.6.1 Uptake of Proteins by Lipid Raft-Dependent Macropinocytosis 164
8.6.2 Points of Consideration for the Use of CPPs 165
8.7 Classification of Therapeutic Peptides 167
8.7.1 Bioactive Peptides 167
8.7.2 Peptide Aptamers 168
8.7.3 Designed Peptides 171
8.7.4 Antibodies 172
8.8 Production and Administration of Therapeutic Peptides In Vivo 172
8.8.1 Extracellular Protein Therapeutics and Peptides with Extracellular
Targets 172
8.8.2 Peptides Targeting Intracellular Targets In Vivo 173
8.9 Concluding Remarks 175
References 176
9 Peptide Arrays on Solid Supports: A Tool for the Identification
of Peptide Ligands 187
Mike Schutkowski, Alexandra Thiele, and Joachim Koch
9.1 Introduction 187
9.2 Synthesis of Peptide Arrays 188
I
9.2.1 Fmoc-Based Synthesis of Peptides on Cellulose Membranes 188
9.2.2 Fabrication of CelluSpots 190
9.2.3 Generation of Peptide Arrays with a Laser Printer 191
9.2.4 Generation of Peptide Arrays on a Compact Disc Device 191
9.2.5 Generation of Peptide Arrays by Chemoselective Immobilization 191
9.3 Applications of Peptide Arrays 293
9.3.1 Generation of Small Amounts of Soluble Peptide Libraries 193
9.3.2 Epitope Mapping of Monoclonal Antibodies 194
9.3.3 Investigation of Antibody Epitopes in Polyclonal Sera 195
9.3.4 Investigation of Protein-Protein Interactions 196
9.3.4.1 General Considerations 196
9.3.4.2 Identification of Enzyme Substrates 197
9.3.5 Mapping of Protein-Nucleic Acid Interactions 202
9.3.6 Screening for Antimicrobial Peptides 202
9.3.7 Identification, Characterization, and Optimization of Peptidic
Ligands 204
9.3.8 Identification of Metal Ion-Selective Peptides 204
9.4 Challenges in High-Throughput Screening (HTS) 205
9.5 Future Perspectives 206
Acknowledgments 207
Abbreviations 207
References 207
Index 219 |
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| spelling | Peptides as drugs discovery and development ed. by Bernd Groner Weinheim WILEY-VCH-Verl. 2009 XV, 226 S. Ill., graph. Darst. 25 cm txt rdacontent n rdamedia nc rdacarrier Literaturangaben Drug Discovery Drugs Design HIV Infections drug therapy Neoplasms drug therapy Peptide drugs Peptides physiology Arzneimittel (DE-588)4003115-9 gnd rswk-swf Targeted drug delivery (DE-588)4302415-4 gnd rswk-swf Peptide (DE-588)4045125-2 gnd rswk-swf Peptide (DE-588)4045125-2 s Arzneimittel (DE-588)4003115-9 s Targeted drug delivery (DE-588)4302415-4 s DE-604 Groner, Bernd (DE-588)133071413 edt text/html http://deposit.dnb.de/cgi-bin/dokserv?id=3192370&prov=M&dok_var=1&dok_ext=htm Inhaltstext HBZ Datenaustausch application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=018665455&sequence=000004&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA Inhaltsverzeichnis |
| spellingShingle | Peptides as drugs discovery and development Drug Discovery Drugs Design HIV Infections drug therapy Neoplasms drug therapy Peptide drugs Peptides physiology Arzneimittel (DE-588)4003115-9 gnd Targeted drug delivery (DE-588)4302415-4 gnd Peptide (DE-588)4045125-2 gnd |
| subject_GND | (DE-588)4003115-9 (DE-588)4302415-4 (DE-588)4045125-2 |
| title | Peptides as drugs discovery and development |
| title_auth | Peptides as drugs discovery and development |
| title_exact_search | Peptides as drugs discovery and development |
| title_full | Peptides as drugs discovery and development ed. by Bernd Groner |
| title_fullStr | Peptides as drugs discovery and development ed. by Bernd Groner |
| title_full_unstemmed | Peptides as drugs discovery and development ed. by Bernd Groner |
| title_short | Peptides as drugs |
| title_sort | peptides as drugs discovery and development |
| title_sub | discovery and development |
| topic | Drug Discovery Drugs Design HIV Infections drug therapy Neoplasms drug therapy Peptide drugs Peptides physiology Arzneimittel (DE-588)4003115-9 gnd Targeted drug delivery (DE-588)4302415-4 gnd Peptide (DE-588)4045125-2 gnd |
| topic_facet | Drug Discovery Drugs Design HIV Infections drug therapy Neoplasms drug therapy Peptide drugs Peptides physiology Arzneimittel Targeted drug delivery Peptide |
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