The first and only guide to showcase the impact of phage display technology on drug discovery, this reference details the theories, principles, and methods impacting the field and demonstrates applications for peptide phage display, protein phage display, and the development of novel antibodies. Highlighting the current and future role of phage display in the development of protein therapeutics, this book provides a comprehensive overview that will prove invaluable to anyone researching recombinant antibodies. Daniel E. Levy, editor of the Drug Discovery Series, is the founder of DEL BioPharma, a consulting service for drug discovery programs. He also maintains a blog that explores organic chemistry.

Table of Contents

Contents Filamentous Bacteriophage Structure and Biology, D.J. Rodi, S. Mandava, and L. Makowski Introduction Taxonomy and Genetics Viral Gene Products Structure of the Virion Filamentous Bacteriophage Life Cycle Phage Library Diversity Biological Bottlenecks: Sources of Library Censorship Quantitative Diversity Estimation Improved Library Construction Vectors and Modes of Display, V.A. Petrenko and G.P. Smith Introduction Most Display Vectors are Based on Filamentous Phage General Cloning Vectors Based on Filamentous Phage Classification of Filamentous Phage Display Systems Phage f1-The First Phage-Display Vector Low DNA Copy Number Display Vectors Based on Fd-Tet Diversity of Type 3 Vectors Type 8 Vectors: First Lessons Mosaic Display in Type nn Systems Mosaic Display in Phagemid Systems Vectors for C-Terminal Display Phage Proteins as Constraining Scaffolds Conclusion Methods for the Construction of Phage-Displayed Libraries, F.A. Fellouse and G. Pal Introduction Oligonucleotide-Directed Mutagenesis Random Mutagenesis Combinatorial Infection and Recombination DNA Shuffling Selection and Screening Strategies, M.S. Dennis Introduction General Considerations The Selection Process Selections Methods Phage Library for Developing Antibody-Targeted Diagnostics and Vaccines, N.E. van Houten and J.K. Scott Introduction Phage-Display Libraries as Tools for Epitope Discovery Diagnostics Phage Libraries for Epitope Mapping Phage Display Libraries for Vaccine Development Developing Immunogens From Peptide Leads Summary Conclusion Abbreviations Exploring Protein-Protein Interactions Using Peptide Libraries Displayed on Phage, K. Deshayes Introduction Extracellular Protein-Protein Interactions Intracellular Protein-Protein Interactions Conclusions Substrate Phage Display, S. Ohkubo Overview Introduction The Concept of Substrate Phage Display Application of Substrate Phage Display to Cancer Research Conclusions Mapping Intracellular Protein Networks, Z. Han, E. Karatan, and B.K. Kay Introduction Domain-Mediated Interactions Nondomain Mediated Protein-Protein Interactions Software for Identifying Candidate Interacting Partners Analyzing Predicted Interactions Relevance to Biotechnology and Drug Discovery High Throughput and High Content Screening Using Peptides, R.O. Carlson, R. Hyde-DeRuyscher, and P.T. Hamilton Introduction Peptides as Enzyme Inhibitors Peptides as Conformational Probes Summary Engineering Protein Folding and Stability, M. Tuna and D.N. Woolfson Protein Redesign and Design Early Combinatorial Studies Aimed at Repacking the Cores of Proteins Phage Display in Engineering Protein Stability A Worked Example: Repacking the Hydrophobic Core of Ubiquitin Studies that Build on the Original Methods Summary Identification of Natural Protein-Protein Interactions with cDNA Libraries, R. Crameri, C. Rhyner, M. Weichel, S. Fluckiger, and Z. Konthur Overview Introduction Cloning Vectors Display of cDNA Libraries on Phage Surface Problems Associated with the Display of cDNA Libraries on Phage Surface Adaptability of Phage Display to High-Throughput Screening Technology Conclusions Mapping Protein Functional Epitopes, S.K. Avrantinis and G.A. Weiss Introduction Single Point Alanine Mutagenesis Combinatorial Site-Specific Mutagenesis Other Approaches to Phage-Displayed Functional Epitope Mapping Conclusion Selections for Enzymatic Catalysts, J. Bertschinger, C. Heinis, and D. Neri Introduction Selection Methods Discussion Antibody Humanization and Affinity Maturation Using Phage Display, J.S. Marvin and H.B. Lowman Introduction Humanization Using Phage Display In Vitro Affinity Maturation of Antibodies Emerging Approaches Conclusions Antibody Libraries from Immunized Repertoires, J.D. Berry and M. Popkov Introduction Immune Antibody Library Construction Immune Antibody Library Selection The Future Acknowledgements Naive Antibody Libraries from Natural Repertoires, C.L. Dobson, R.R. Minter, and C.P. Hart-Shorrock Introduction Construction of Naive Libraries Applications of Naive Libraries Synthetic Antibody Libraries, F.A. Fellouse and S.S. Sidhu Introduction The Scripps Research Institute The Medical Research Council Morphosys Genentech Conclusions Index