Synthesis and biological evaluation of non-isomerizable analogues of Ala-tRNA(Ala)

Org Biomol Chem. 2013 Sep 28;11(36):6161-9. doi: 10.1039/c3ob41206g.

Abstract

Aminoacyl-tRNAs serve as amino acid donors in many reactions in addition to protein synthesis by the ribosome, including synthesis of the peptidoglycan network in the cell wall of bacterial pathogens. Synthesis of analogs of aminoacylated tRNAs is critical to further improve the mechanism of these reactions. Here we have described the synthesis of two non-isomerizable analogues of Ala-tRNA(Ala) containing an amide bond instead of the isomerizable ester that connects the amino acid with the terminal adenosine in the natural substrate. The non-isomerizable 2' and 3' regioisomers were not used as substrates by FemX(Wv), an alanyl-transferase essential for peptidoglycan synthesis, but inhibited this enzyme with IC50 of 5.8 and 5.5 μM, respectively.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Dose-Response Relationship, Drug
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Models, Molecular
  • Molecular Conformation
  • Nitrogenous Group Transferases / antagonists & inhibitors*
  • Nitrogenous Group Transferases / metabolism
  • RNA, Transfer, Ala / chemical synthesis*
  • RNA, Transfer, Ala / chemistry
  • RNA, Transfer, Ala / pharmacology*
  • Structure-Activity Relationship

Substances

  • Enzyme Inhibitors
  • RNA, Transfer, Ala
  • Nitrogenous Group Transferases