A New Generic Method for the Production of Protein-Based Inhibitors of Proteins Involved in Cancer Metastasis.

Abstract

Our objective is to develop a general method to make protein-based inhibitors against?protein targets and as the test case to a proteinase involved in metastasis, stromelysin. The idea is to use a binding epitope display framework which should bind preferentially to the active site pocket of target proteins and which would he screened against targets using phage display. Having spent a lot of effort constructing vectors to generate an expression vector for stromelysin we have now found a source via a collaboration with Dr. Ye at Parke-Davis. Library construction has turned out to more difficult than expected. We have now turned to a construction tecnology which can be applied to any portion of the framework independent of the presence of restriction sites. We have screened a peptide library against stromelysin and this has yielded binders whose sequences have been determined. This year we have also succeeded in constructing our first library in an aglin based framework. As part of our efforts to charaterize the binding epitope display framework molecule which we use, eglin c, we have also developed and verified a new method for using mutagenesis to study protein structure which we call patterned library analysis.

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Document Details

Document Type
Technical Report
Publication Date
Sep 01, 1997
Accession Number
ADA337506

Entities

People

  • Marshall H. Edgell

Organizations

  • University of North Carolina at Chapel Hill

Tags

DTIC Thesaurus Topics

  • Amino Acids
  • Biochemistry
  • Biomedical Research
  • Cancer
  • Chemical Synthesis
  • Chemistry
  • Construction
  • Engineering
  • Equations
  • Genetic Structures
  • Heat Capacity
  • Inhibitors
  • Materials
  • Metastasis
  • Molecules
  • Neoplasms
  • North Carolina

Readers

  • Molecular Genetics
  • Molecular and Cellular Biochemistry