Inhibition of vaccinia RNA guanine 7-methyltransferase by compounds designed as multisubstrate adducts.

Several potential inhibitors of mRNA guanine 7-methyltransferase, which were designed from mechanism-based considerations, were evaluated against the vaccinia virus capping enzyme complex. Of the compounds tested, 5'-deoxy-5'[6-(2-aminopyrrolo[2,3-d]-pyrimidine-4-one) methylthio]adenosine (9) had good selective inhibitory activity against vaccinia mRNA guanine 7-methyltransferase, exhibiting an IC50 of 9.2 X 10(-5) M. Structure-activity considerations suggest that specific inhibition of RNA methyltransferases by low molecular weight multisubstrate adduct inhibitors may be achievable.