Design, synthesis and evaluation of analogs of initiation factor 4E (eIF4E) cap-binding antagonist Bn7-GMP.

ABSTRACT: Aberrant regulation of cap-dependent translation has been frequently observed in the development of cancer. Association of the cap-binding protein eIF4E with N(7)-methylated guanosine capped mRNA is the rate limiting step governing translation initiation; and therefore represents an attractive process for cancer drug discovery. Previously, replacement of the 7-Me group of the Me(7)-guanosine monophosphate with a benzyl group has been found to increase binding affinity to eIF4E. Recent X-ray crystallographic studies have revealed that the cap-binding pocket undergoes a unique structural change in order to accommodate the benzyl group. To explore the structure-activity relationships governing the affinity of N(7)-benzylated guanosine monophosphate (Bn(7)-GMP) for eIF4E, we virtually screened

SUBMITTER: Jia Y 

PROVIDER: S-EPMC2853597 | biostudies-literature | 2010 Apr

REPOSITORIES: biostudies-literature