Inhibition of Escherichia coli glucosamine synthetase by novel electrophilic analogues of glutamine--comparison with 6-diazo-5-oxo-norleucine

Bioorg Med Chem Lett. 2000 Dec 18;10(24):2795-8. doi: 10.1016/s0960-894x(00)00565-5.

Abstract

A series of electrophilic glutamine analogues based on 6-diazo-5-oxo-norleucine has been prepared, using novel synthetic routes, and evaluated as inhibitors of Escherichia coli glucosamine synthetase. The gamma-dimethylsulphonium salt analogue of glutamine was found to be one of the most potent inactivators of this enzyme yet reported, with an apparent second order rate constant (k2/Ki) of 3.5 x 10(5) M(-1) min(-1).

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antimetabolites, Antineoplastic / pharmacology
  • Diazooxonorleucine / pharmacology
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology
  • Escherichia coli / enzymology*
  • Glutamine / analogs & derivatives*
  • Glutamine / chemical synthesis
  • Glutamine / pharmacology*
  • Glutamine-Fructose-6-Phosphate Transaminase (Isomerizing) / antagonists & inhibitors*
  • Glutamine-Fructose-6-Phosphate Transaminase (Isomerizing) / metabolism
  • Kinetics
  • Static Electricity
  • Structure-Activity Relationship
  • Sulfides

Substances

  • Antimetabolites, Antineoplastic
  • Enzyme Inhibitors
  • Sulfides
  • Diazooxonorleucine
  • Glutamine
  • Glutamine-Fructose-6-Phosphate Transaminase (Isomerizing)
  • dimethyl sulfide