Substrate/inhibition studies of bacteriophage T7 RNA polymerase with the 5'-triphosphate derivative of a ring-expanded ('fat') nucleoside possessingpotent antiviral and anticancer activities

As part of an effort to explore the mechanism of potent, broad spectrum ant iviral and anticancer activities of a number of ring-expanded ('fat') nucle osides that we recently reported, a representative 'fat' nucleoside 4,6-dia mino-8-imino-8H-1-beta-D-ribofuranosylimidazo[4,5-e][1,3]diazepin (1) was c onverted to its T-triphosphate derivative (2), and biochemically screened f or possible inhibition of nucleic acid polymerase activity, employing synth etic DNA templates and the bacteriophage T7 RNA polymerase as a representat ive polymerase. Our results suggest that 2 is a moderate inhibitor of T7 RN A polymerase, and that the 5'-triphosphate moiety of 2 appears to be essent ial for inhibition as nucleoside 1 alone failed to inhibit the polymerase r eaction. (C) 1999 Elsevier Science Ltd. All rights reserved.