Substrate/inhibition studies of bacteriophage T7 RNA polymerase with the 5′-triphosphate derivative of a ring-expanded (‘fat’) nucleoside possessing potent antiviral and anticancer activities

Abstract As part of an effort to explore the mechanism of potent, broad spectrum antiviral and anticancer activities of a number of ring-expanded (‘fat’) nucleosides that we recently reported, a representative ‘fat’ nucleoside 4,6-diamino-8-imino-8 H -1-β- d -ribofuranosylimidazo[4,5- e ][1,3]diazepine ( 1 ) was converted to its 5′-triphosphate derivative ( 2 Download high-res image (60KB) Download full-size image Scheme 2 . ), and biochemically screened for possible inhibition of nucleic acid polymerase activity, employing synthetic DNA templates and the bacteriophage T7 RNA polymerase as a representative polymerase. Our results suggest that 2 is a moderate inhibitor of T7 RNA polymerase, and that the 5′-triphosphate moiety of 2 appears to be essential for inhibition as nucleoside Scheme 1 , Scheme 2 Download high-res image (36KB) Download full-size image Scheme 1 . alone failed to inhibit the polymerase reaction.