Combinatorial Libraries

Synthesis, Screening and Application Potential

Riccardo Cortese

• Publisher: De Gruyter
• Year: 2013
• Print ISBN: 9783110143959
• eBook ISBN: 9783110808902
• Edition: 1
• Topic: Biological Sciences
• Subtopic: Biochemistry
• Index: Biological Sciences

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Table of contents

• A Synthetic Peptide Libraries
• 1 Soluble Synthetic Combinatorial Libraries: The Use of Molecular Diversities for Drug Discovery
• 1.1 Introduction
• 1.2 Synthetic Combinatorial Libraries (SCLs)
• 1.3 Synthetic Methods for the Generation of SCLs
• 1.4 SCLs in Drug Discovery and Basic Research
• 1.5 Conclusion
• 2 Combinatorial Libraries of Synthetic Structures: Synthesis, Screening, and Structure Determination
• 2.1 Introduction
• 2.2 One-Bead One-Structure Concept
• 2.3 Design and Synthesis of Non-Peptide Libraries
• 2.4 Release Assay
• 2.5 Stucture Determination
• 2.6 Conclusion
• 3 Peptide Libraries Bound to Continuous Cellulose Membranes: Tools to study Molecular Recognition
• 3.1 Introduction
• 3.2 Detection of antibody epitopes
• 3.3 Mutational analyses of peptide epitopes
• 3.4 Positional scanning combinatorial library
• 3.5 Indentification of metal binding peptides
• 3.6 Summary
• B Nucleic Acids Libraries
• 4 In Vitro Selection of Nucleic Acid Sequences that Bind Small Molecules
• 4.1 Introduction
• 4.2 Natural RNA Receptors
• 4.3 In Vitro Selection
• 4.4 Amino Acid Aptamers
• 4.5 Cofactors
• 4.6 DNA Aptamers
• 4.7 The Complexity of Complexity
• 4.8 Aptamer Structures
• 4.9 Transition State Stabilization and Tight Binding
• 4.10 Conclusions
• 5 Discovery and Characterization of a Thrombin Aptamer Selected from a Combinatorial ssDNA Library
• 5.1 Introduction
• 5.2 Discovery and Initial Characterization
• 5.3 Structure
• 5.4 Binding Site on Thrombin
• 5.5 Determination of Kd and Ki
• 5.6 In vitro Activity
• 5.7 In Vitro Activity
• 5.8 Conclusions
• C Phage Display of Peptide Libraries
• 6 Structural and Functional Constraints in the Display of Peptides on Filamentous Phage Capsids
• 6.1 Introduction
• 6.2 The Phage Life Cycle
• 6.3 A Low Resolution Model
• 6.4 Extending the Amino-Terminus of pVIII
• 6.5 Modifying the Surface of Filamentous Phage by Amino Acid Substitution
• 6.6 Can the Remaining Minor Proteins Support Modification?
• 7 Conformationally Defined Peptide Libraries on Phage: Selectable Templates for the Design of Pharmacological Agents
• 7.1 Introduction
• 7.2 From Peptides to Peptidomimetics
• 7.3 Building Constraints in Phage-Displayed Polypeptides
• 7.4 The Minibody: An Engineered ß-Pleated Scaffold for the Display of Reverse-Turn Motifs
• 7.5 The Zinc Finger: A Small Domain for the Display of Structurally Homogeneous α-Helical Motifs
• 7.6 Future Developments: Progressing Toward Non-Peptide Pharmaceuticals
• 8 Discovery of Disease-Specific Mimotopes by Screening Phage Libraries with Human Serum Samples
• 8.1 Introduction
• 8.2 Using Polyclonal Antibodies as a Ligate for the Selection of RPL
• 8.3 Immunofingerprint of the Individual Humoral Response to an Infectious Agent: The Hepatitis C Virus
• 8.4 Phagotope-Based Vaccines
• 8.5 Toward the Indentification of the Pathological Antigens of Autoimmune Diseases
• 8.6 Conclusions
• 9 The Utilization of Platelets and Whole Cells for the Selection of Peptides Ligands from Phage Display Libraries
• 9.1 Introduction
• 9.2 Platelets
• 9.3 Urokinase Plasminogen Activator Receptor
• 9.4 Fibroblast Growth Factor Receptor 1
• 10 Identification of MHC Binding Motifs with Synthetic and Phage Displayed Peptide Libraries
• 10.1 Introduction
• 10.2 Identification of MHC Class II Peptide Binding Motifs
• 10.3 Conserved and Allele-Specific Anchor Residues Explain Promiscuity and Allele Specificity of HLA-DR/Peptide Interaction
• 10.4 High-Stringency Screening and the Design of Short Peptide Antagonists
• 10.5 Anchor Residues Interact with Pockets of the MHC Class II Peptide Binding Cleft
• 10.6 Refinement of Peptide Motifs and Prediction of MHC Class II/Peptide Interaction
• 10.7 Changing the Fine Specificity of a Class II MHC Pocket
• 10.8 Peptide Libraries and MHC: An Outlook
• D Phage Display of Protein Domains
• 11 Isolating High Affinity Human Antibodies from Phage Repertoires
• 11.1 Introduction
• 11.2 High Affinity Human Antibodies to RT3
• 11.3 Discussion
• 11.4 Conclusion
• 12 Altering the Function of Enzymes and Macromolecular Inhibitors by Phage Display
• 12.1 Introduction
• 12.2 Background
• 12.3 Filamentous Phage Display System
• 12.4 Enzymes Displayed on Phage
• 12.5 Macromolecular Protease Inhibitors Displayed on Phage
• 12.6 Conclusions
• Authors
• Index