Phage Display In Biotechnology and Drug Discovery

Phage Display In Biotechnology and Drug Discovery

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ISBN 9780824754662
Cat# DK2163
 

Features

  • Describes the basic principles of phage display and the methods and systems which have been developed for key applications
  • Outlines applications for peptide phage display in the development of vaccines and high throughput screens, as well as the exploration of protein–protein interactions and enzyme substrate characteristics
  • Details the use of phage display in the engineering of protein stability, the identification and mapping of protein–protein interactions, and the development of catalysts
  • Provides broad coverage of the impact of phage display technology on the development of protein therapeutics
  • Shows how phage display and antibody libraries have been used to develop and improve therapeutic production
  • Presents expert opinions on future challenges in the field
  • Summary

    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. Flückiger, 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
    Naïve Antibody Libraries from Natural Repertoires, C.L. Dobson, R.R. Minter, and C.P. Hart-Shorrock
    Introduction
    Construction of Naïve Libraries
    Applications of Naïve Libraries
    Synthetic Antibody Libraries, F.A. Fellouse and S.S. Sidhu
    Introduction
    The Scripps Research Institute
    The Medical Research Council
    Morphosys
    Genentech
    Conclusions Index

    Editorial Reviews

    “… The book covers broadly all aspects of phage-display technology and will be highly appreciated by those working with this technique and interested in applications. … The book is a clear invitation to use the phage-display technique both in biotechnology and drug discovery; … this is a very comprehensive book demonstrating the versatility and the value of phage display in many applications. It is clearly written giving an interesting historical background to many presently used variations on the phage-display technique.”
    —Wim Quax, Rijksuniversiteit Groningen, The Netherlands, in ChemBioChem, Vol. 7, No. 699 - 703

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