Glutamyl-gamma-boronate inhibitors of bacterial Glu-tRNA(Gln) amidotransferase

Bioorg Med Chem Lett. 2001 Sep 17;11(18):2561-4. doi: 10.1016/s0960-894x(01)00499-1.

Abstract

Analogues of glutamyl-gamma-boronate (1) were synthesized as mechanism-based inhibitors of bacterial Glu-tRNA(Gln) amidotransferase (Glu-AdT) and were designed to engage a putative catalytic serine nucleophile required for the glutaminase activity of the enzyme. Although 1 provides potent enzyme inhibition, structure-activity studies revealed a narrow range of tolerated chemical changes that maintained activity. Nonetheless, growth inhibition of organisms that require Glu-AdT by the most potent enzyme inhibitors appears to validate mechanism-based inhibitor design of Glu-AdT as an approach to antimicrobial development.

MeSH terms

  • Anti-Infective Agents / chemistry*
  • Anti-Infective Agents / pharmacology*
  • Boronic Acids / chemistry*
  • Boronic Acids / pharmacology*
  • Drug Evaluation, Preclinical
  • Enzyme Inhibitors / chemistry*
  • Enzyme Inhibitors / pharmacology*
  • Inhibitory Concentration 50
  • Microbial Sensitivity Tests
  • Nitrogenous Group Transferases / antagonists & inhibitors*
  • Structure-Activity Relationship

Substances

  • Anti-Infective Agents
  • Boronic Acids
  • Enzyme Inhibitors
  • glutamyl-gamma-boronate
  • Asp-tRNA(Asn) amidotransferase
  • Nitrogenous Group Transferases