Design and synthesis of a mimetic from an antibody complementarity-determining region

Science. 1991 Aug 16;253(5021):792-5. doi: 10.1126/science.1876837.

Abstract

A technique for producing non-peptide compounds (mimetics) of designed specificities was developed that permitted the synthesis of a conformationally restricted molecule that mimicked the binding and functional properties of monoclonal antibody (MAb) 87.92.6, which recognizes the reovirus type 3 cellular receptor. Binding of either MAb 87.92.6, peptide analogs, or 87.1-mimetic to the cellular receptor inhibited cellular proliferation. The mimetic was a synthetic beta-loop structure that mimics the second complementarity-determining region of the MAb. These studies may lead to strategies for the synthetic design of antibody complementarity regions, ligands, and other pharmacologically active agents that are water soluble, resistant to proteolysis, and nonimmunogenic.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Antibodies, Monoclonal / chemistry*
  • Cell Division / drug effects
  • Drug Design
  • Endopeptidases / pharmacology
  • Mammalian orthoreovirus 3
  • Models, Molecular
  • Molecular Conformation
  • Peptides / metabolism
  • Piperidines / chemical synthesis
  • Piperidines / chemistry*
  • Piperidines / pharmacology
  • Receptors, Virus / drug effects
  • Receptors, Virus / immunology*
  • Receptors, Virus / metabolism
  • Structure-Activity Relationship

Substances

  • Antibodies, Monoclonal
  • Peptides
  • Piperidines
  • Receptors, Virus
  • Endopeptidases