(S)-Thiirancarboxylic acid as a reactive building block for a new class of cysteine protease inhibitors

Bioorg Med Chem Lett. 2000 Dec 4;10(23):2647-51. doi: 10.1016/s0960-894x(00)00549-7.

Abstract

For (S)-thiirancarboxylic acid a second-order rate constant of k2nd = 222 M(-1) min(-1) for the irreversible inhibition of papain was determined. The ethyl and methyl ester do not inhibit the enzyme time-dependently. An improved synthesis of enantiomerically pure thiirancarboxylic acid is described. It is shown that thiirancarboxylates can be substrates for serine proteases (alpha-chymotrypsin) and esterases (pig liver esterase) and even for metallo proteases (thermolysin).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carboxylic Acids / chemistry*
  • Carboxylic Acids / metabolism
  • Chymotrypsin / metabolism
  • Cysteine Proteinase Inhibitors / chemistry
  • Cysteine Proteinase Inhibitors / pharmacology*
  • Esterases / metabolism
  • Heterocyclic Compounds / chemistry*
  • Heterocyclic Compounds / metabolism
  • Liver / enzymology
  • Substrate Specificity
  • Swine
  • Thermolysin / metabolism

Substances

  • Carboxylic Acids
  • Cysteine Proteinase Inhibitors
  • Heterocyclic Compounds
  • thiirancarboxylic acid
  • Esterases
  • Chymotrypsin
  • alpha-chymotrypsin
  • Thermolysin