Synthesis and evaluation of potential inhibitors of eIF4E cap binding to 7-methyl GTP

Bioorg Med Chem Lett. 2005 Apr 15;15(8):2177-80. doi: 10.1016/j.bmcl.2005.01.080.


Cap-dependent translation is initiated by the binding of eIF4E to capped mRNA (m(7)GpppN). We have prepared a small library of 7-methyl guanosine nucleoside and nucleotide analogs and evaluated their ability to inhibit eIF4E binding to 7-methyl GTP with a competitive eIF4E binding immunoassay. 5'-H-Phosphonate derivatives in which the 2'- and 3'-riboside hydroxyls were tethered together by an isopropylidene group were shown to be a new class of inhibitors of eIF4E binding to capped mRNA.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 3T3 Cells
  • Animals
  • Binding, Competitive
  • Drug Evaluation, Preclinical / methods
  • Eukaryotic Initiation Factor-4E / antagonists & inhibitors*
  • Eukaryotic Initiation Factor-4E / metabolism*
  • Mice
  • Protein Binding / physiology
  • RNA Cap Analogs / antagonists & inhibitors*
  • RNA Cap Analogs / metabolism*


  • Eukaryotic Initiation Factor-4E
  • RNA Cap Analogs
  • 7-methylguanosine triphosphate