Ester and hydroxamate analogues of methionyl and isoleucyl adenylates as inhibitors of methionyl-tRNA and isoleucyl-tRNA synthetases

Bioorg Med Chem Lett. 2001 Apr 23;11(8):961-4. doi: 10.1016/s0960-894x(01)00095-6.

Abstract

The structure activity relationship on a series of ester and hydroxamate analogues of methionyl and isoleucyl adenylate has been investigated through introducing linkers between the 1'-position of ribose and adenine surrogates as methionyl-tRNA, and isoleucyl-tRNA synthetase inhibitors, respectively. The results indicate that ester analogue 23 was found to be a potent inhibitor of Escherichia coli methionyl-tRNA synthetase, and its interaction with the active site was proposed by a molecular modeling study.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine / analogs & derivatives
  • Adenosine / chemical synthesis
  • Adenosine / pharmacology*
  • Adenosine Monophosphate / analogs & derivatives*
  • Adenosine Monophosphate / chemical synthesis
  • Adenosine Monophosphate / pharmacology*
  • Binding Sites / physiology
  • Escherichia coli
  • Esters / chemical synthesis
  • Hydroxamic Acids / chemical synthesis
  • Isoleucine / chemical synthesis
  • Isoleucine-tRNA Ligase / antagonists & inhibitors*
  • Methionine / analogs & derivatives*
  • Methionine / chemical synthesis
  • Methionine / pharmacology*
  • Methionine-tRNA Ligase / antagonists & inhibitors*
  • Models, Molecular
  • Structure-Activity Relationship

Substances

  • Esters
  • Hydroxamic Acids
  • Isoleucine
  • methioninyl adenylate
  • Adenosine Monophosphate
  • Methionine
  • Methionine-tRNA Ligase
  • Isoleucine-tRNA Ligase
  • Adenosine