Towards an Alternative for Antibodies: Construction and Characterization of a Large Combinatorial Library of Diverse Binding Proteins

Abstract

The goal of this to create a large and very diverse population of binding proteins from which individual members can be selected on the basis of target specificity and be used as a substitute for antibodies in biosensor and other applications. Toward this end, phage display technology was used to create a collection of seventeen distinct combinatorial libraries in which the binding surfaces of several small, stable parent proteins were randomized. The completed collection contains approximately 4x10(exp 9) different protein variants. Because of the types of parent molecules chosen and because of the way the libraries were designed, the variants are expected to have more physical stability than antibody molecules and to be able to function in more severe types of environments. In a test of the general binding properties of the collection, the library pool was taken through four rounds of panning against 31 randomly chosen test compounds (20 proteins, 4 peptides and 7 small molecules) . Apparent binding proteins were observed against 22/31 (71%) of the compounds tested (17 proteins, 2 peptides and 3 small organic molecules) indicating the library collection is a useful source of receptor proteins.

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Document Details

Document Type
Technical Report
Publication Date
Jan 01, 2001
Accession Number
ADA394001

Entities

People

  • David Baker

Organizations

  • University of Washington

Tags

Communities of Interest

  • Biomedical

DTIC Thesaurus Topics

  • Amines
  • Amino Acids
  • Bacterial Proteins
  • Biomedical And Dental Materials
  • Chemical Reactions
  • Chemical Synthesis
  • Chemistry
  • Computer Simulations
  • Mass Spectrometry
  • Molecular Biology
  • Molecular Dynamics
  • Polymer Chemistry
  • Polymeric Films
  • Proteins
  • Proteomics

Fields of Study

  • Biology

Readers

  • Distributed Systems and Data Platform Development
  • Molecular and Cellular Biochemistry

Technology Areas

  • Biotechnology