A bireactant, irreversible, active-site-directed inhibitor of beta-D-galactosidase (Escherichia coli). Synthesis and properties of (1/2,5,6)-2-(3-azibutylthio)-5,6-epoxy-3-cyclohexen-1-ol

Carbohydr Res. 1991 Jul 18;214(1):35-41. doi: 10.1016/s0008-6215(00)90528-7.

Abstract

(1/2,5,6)-2-(3-Azibutylthio)-5,6-epoxy-3-cyclohexen-1-ol (1) was synthesized and was found to irreversibly inactivate beta-D-galactosidase (Escherichia coli). The inactivation was prevented by the presence of isopropyl 1-thio-beta-D-galactopyranoside (IPTG). The vinyloxirane group of 1 reacted with water and other nucleophiles, especially at higher pH values. Reaction of 1 with beta-D-galactosidase was slow enough so that a competitive-inhibition constant (Ki) of 29mM could be determined. The inhibition constant for (1,2/3,6)-6-(3-azibutylthio)-2-bromo-4-cyclohexene-1,3-diol (2), the precursor of the bireactant inhibitor 1, was 13 mM, while that of (1,3/2,4)-3-(3-azibutylthio)-5-cyclohexene-1,2,4-triol (3), the product formed when the reactant is allowed to react with water, was 23mM. After irradiation by light, beta-D-galactosidase that had initially been treated with the bireactant compound and then digested with trypsin, showed a new pattern of elution from h.p.l.c., indicating that there was reaction at two regions of the beta-D-galactosidase molecule.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Azo Compounds / chemical synthesis
  • Azo Compounds / chemistry
  • Azo Compounds / pharmacology*
  • Binding Sites
  • Cyclohexanols / chemical synthesis
  • Cyclohexanols / chemistry
  • Cyclohexanols / pharmacology*
  • Escherichia coli / enzymology
  • Isopropyl Thiogalactoside
  • Kinetics
  • beta-Galactosidase / antagonists & inhibitors*

Substances

  • Azo Compounds
  • Cyclohexanols
  • 2-(3-azibutylthio)-5,6-epoxy-3-cyclohexen-1-ol
  • Isopropyl Thiogalactoside
  • beta-Galactosidase