Combinatorial Libraries: Synthesis, Screening and Application PotentialRiccardo Cortese No detailed description available for "Combinatorial Libraries". |
Contents
| 1 | |
| 2 | |
| 6 | |
| 12 | |
15 Conclusion | 21 |
Synthesis Screening and Structure Determination | 27 |
22 OneBead OneStructure Concept | 28 |
23 Design and Synthesis of NonPeptide Libraries | 29 |
65 Modifying the Surface of Filamentous Phage by Amino Acid Substitution | 122 |
66 Can the Remaining Minor Proteins Support Modification? | 123 |
Selectable Templates for the Design of Pharmacological Agents | 127 |
72 From Peptides to Peptidomimetics | 128 |
73 Building Constraints in PhageDisplayed Polypeptides | 129 |
An Engineered ßPleated Scaffold for the Display of ReverseTurn Motifs | 130 |
A Small Domain for the Display of Structurally Homogeneous αHelical Motifs | 135 |
Progressing Toward NonPeptide Pharmaceuticals | 137 |
24 Release Assay | 35 |
25 Stucture Determination | 41 |
26 Conclusion | 47 |
Tools to study Molecular Recognition | 53 |
32 Detection of antibody epitopes | 54 |
33 Mutational analyses of peptide epitopes | 56 |
34 Positional scanning combinatorial library | 57 |
35 Indentification of metal binding peptides | 60 |
36 Summary | 66 |
B Nucleic Acids Libraries | 69 |
43 In Vitro Selection | 71 |
44 Amino Acid Aptamers | 73 |
45 Cofactors | 75 |
46 DNA Aptamers | 77 |
48 Aptamer Structures | 78 |
49 Transition State Stabilization and Tight Binding | 81 |
410 Conclusions | 84 |
5 Discovery and Characterization of a Thrombin Aptamer Selected from a Combinatorial ssDNA Library | 87 |
52 Discovery and Initial Characterization | 88 |
53 Structure | 92 |
54 Binding Site on Thrombin | 97 |
55 Determination of Kd and Ki | 100 |
56 In vitro Activity | 102 |
57 In Vitro Activity | 104 |
58 Conclusions | 108 |
C Phage Display of Peptide Libraries | 113 |
62 The Phage Life Cycle | 114 |
63 A Low Resolution Model | 117 |
64 Extending the AminoTerminus of pVIII | 118 |
8 Discovery of DiseaseSpecific Mimotopes by Screening Phage Libraries with Human Serum Samples | 145 |
82 Using Polyclonal Antibodies as a Ligate for the Selection of RPL | 146 |
The Hepatitis C Virus | 148 |
84 PhagotopeBased Vaccines | 150 |
85 Toward the Indentification of the Pathological Antigens of Autoimmune Diseases | 152 |
86 Conclusions | 154 |
9 The Utilization of Platelets and Whole Cells for the Selection of Peptides Ligands from Phage Display Libraries | 159 |
93 Urokinase Plasminogen Activator Receptor | 167 |
94 Fibroblast Growth Factor Receptor 1 | 171 |
10 Identification of MHC Binding Motifs with Synthetic and Phage Displayed Peptide Libraries | 175 |
102 Identification of MHC Class II Peptide Binding Motifs | 176 |
103 Conserved and AlleleSpecific Anchor Residues Explain Promiscuity and Allele Specificity of HLADRPeptide Interaction | 178 |
104 HighStringency Screening and the Design of Short Peptide Antagonists | 179 |
105 Anchor Residues Interact with Pockets of the MHC Class II Peptide Binding Cleft | 181 |
107 Changing the Fine Specificity of a Class II MHC Pocket | 185 |
D Phage Display of Protein Domains | 189 |
112 High Affinity Human Antibodies to RT3 | 193 |
113 Discussion | 198 |
114 Conclusion | 201 |
12 Altering the Function of Enzymes and Macromolecular Inhibitors by Phage Display | 205 |
122 Background | 206 |
123 Filamentous Phage Display System | 211 |
124 Enzymes Displayed on Phage | 212 |
125 Macromolecular Protease Inhibitors Displayed on Phage | 215 |
126 Conclusions | 217 |
Authors | 223 |
| 227 | |
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Common terms and phrases
activity affinity maturation affinity selection amino acids amino groups anchor anticoagulation antigen aptamer binding arginine assay bacteriophage beads binders Biol Blondelle catalytic cells Chem chemical Chemistry clones coat protein coding complex compounds diversity domain Dooley ecotin eluted enrichment enzymes epitope Felici fibrinogen Figure filamentous phage function fusion gene Geysen GPIIb-IIIa guanosine heparin hexapeptide high affinity Houghten human antibodies identified immune Immunol inhibition inhibitor interaction isolated Krchňák Lebl ligands linker M13 phage method mimotopes minibody molecular molecules monoclonal antibodies motif mutagenesis mutant Nature nucleic acid oligonucleotides Ostresh peptide binding peptide combinatorial libraries peptide libraries peptide mixtures peptidomimetic phage display phagotopes Pinilla platelet pool positional scanning protease pVIII random receptor repertoire residues resin Ribozyme SCLs screening sequence sera shuffled side chain soluble specific ssDNA strategy structure surface synthesis synthetic peptide Szostak target tertiary structure thrombin aptamer tion trypsin vitro selection vivo