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

Cap-dependent translation is initiated by the binding of eIF4E to capped mRNA (m7GpppN). 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.