N-Alkoxysulfamide, N-hydroxysulfamide, and sulfamate analogues of methionyl and isoleucyl adenylates as inhibitors of methionyl-tRNA and isoleucyl-tRNA synthetases

Bioorg Med Chem Lett. 2003 Mar 24;13(6):1087-92. doi: 10.1016/s0960-894x(03)00020-9.

Abstract

A series of sulfamate surrogates of methionyl and isoleucyl adenylate have been investigated as MetRS and IleRS inhibitors by modifications of the sulfamate linker and adenine moieties. The discovery of 2-iodo Ile-NHSO(2)-AMP (58) as a potent Escherichia coli IleRS inhibitor revealed that a significant hydrophobic interaction between the 2-substituent of Ile-NHSO(2)-AMP and the adenine binding site of IleRS provided its high potency to the enzyme.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / pharmacology*
  • Escherichia coli / drug effects
  • Escherichia coli / enzymology
  • Indicators and Reagents
  • Isoleucine-tRNA Ligase / antagonists & inhibitors*
  • Methionine-tRNA Ligase / antagonists & inhibitors*
  • Models, Molecular
  • Molecular Conformation
  • Sulfonamides / chemical synthesis*
  • Sulfonamides / pharmacology*
  • Sulfonic Acids / chemical synthesis*
  • Sulfonic Acids / pharmacology*
  • Thermus thermophilus / enzymology

Substances

  • Enzyme Inhibitors
  • Indicators and Reagents
  • Sulfonamides
  • Sulfonic Acids
  • Methionine-tRNA Ligase
  • Isoleucine-tRNA Ligase