Synthesis and Anti-Elastase Activity of Amide-Cyclized Peptide Analogs of Alpha1-Antitrypsin,

Abstract

The serine protease inhibitor a1-antitrypsin is the most potent inhibitor of human leukocyte elastase (HLE). The mechanism of inhibition of HLE by a 1-AT has not been clearly defined. We have synthesized linear and side-chain cyclized peptide analogs of the reactive site region of this natural inhibitor in an attempt to mimic its bioactive conformation. The alpha-AT analogs 1-3 enclose the reactive site within a loop defined by an amide bond between glutamic acid and lysine side chains, while peptides are cyclized to stabilize either an alpha-helix or a bend in the enzyme binding region N-terminal to the reactive site.

Document Details

Document Type
Technical Report
Publication Date
Jan 01, 1992
Accession Number
ADP008540

Entities

People

  • Anna Crivici
  • Gilles Lajoie

Organizations

  • University of Waterloo

Tags

DTIC Thesaurus Topics

  • Chemical Compounds
  • Chemical Synthesis
  • Chemistry
  • Enzyme Inhibitors
  • Glutamic Acid
  • Inhibition
  • Inhibitors
  • Leukocytes
  • Massachusetts
  • Terminals

Fields of Study

  • Chemistry

Readers

  • Molecular and Cellular Biochemistry