Telomerase-inhibitory effects of the triphosphate derivatives of some biologically active nucleosides.

Abstract

Telomerase is a ribonucleoprotein reverse transcriptase that uses its internal RNA moiety as a template for synthesis of telomere repeats. To clarify the susceptibility of telomerase to HIV-1 reverse transcriptase inhibitors (RT), we investigated the inhibitory effects of 3'-azido-3'-deoxythymidine 5'-triphosphate (AZTTP), which is known to be a potent HIV-1 RT inhibitor, and acyclovir triphosphate (ACVTP). Lineweaver-Burk plot analyses showed that the inhibition mode of these compounds was competitive with the substrate dNTP counterpart. However, inhibition by AZTTP was weak (Ki = 15 microM, Km of dTTP = 7.1 microM). Interestingly, ACVTP showed considerable inhibition. The Ki value of ACVTP was 5.0 microM, being smaller than the Km of dGTP (12 microM).