The synthesis of azapeptidomimetic beta-lactam molecules as potential protease inhibitors

J Org Chem. 2002 Dec 13;67(25):8962-9. doi: 10.1021/jo026280d.

Abstract

Synthetic methods for the construction of a novel peptidomimetic structure are reported. The structure incorporates a beta-lactam and an azapeptide in a peptide backbone with the intention of generating rationally designed substrate-based protease inhibitors. The beta-lactam is formed by subjecting serine or threonine-azapeptides to Mitsunobu reaction conditions. Importantly, the azapeptidomimetic beta-lactam structure permits extended binding inhibition and the synthetic methods to create tetrapeptidomimetic structures are described.

Publication types

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

MeSH terms

  • Aza Compounds / chemical synthesis*
  • Aza Compounds / chemistry
  • Aza Compounds / pharmacology
  • Binding Sites
  • Binding, Competitive
  • Catalysis
  • Combinatorial Chemistry Techniques*
  • Drug Design
  • Models, Molecular
  • Molecular Mimicry
  • Molecular Structure
  • Oligopeptides / chemical synthesis*
  • Oligopeptides / chemistry
  • Oligopeptides / pharmacology
  • Serine Proteinase Inhibitors / chemical synthesis*
  • Serine Proteinase Inhibitors / chemistry
  • Serine Proteinase Inhibitors / pharmacology
  • Structure-Activity Relationship
  • Substrate Specificity
  • beta-Lactams / chemical synthesis*
  • beta-Lactams / chemistry
  • beta-Lactams / pharmacology

Substances

  • Aza Compounds
  • Oligopeptides
  • Serine Proteinase Inhibitors
  • beta-Lactams