Inhibition of the reverse transcriptase from HIV by 3′-azido-3′-deoxythymidine triphosphate and its threo analogue

Abstract

3′-Azido-3′-deoxythymidine triphosphate ( erythro) and its threo isomer were synthesized and investigated for their inhibition of HIV reverse transcriptase from virus isolate U 937/HTLV-III. The erythro isomer was a competitive inhibitor of the reaction directed by (rA) n (dT) 12–18 and the K i value was 0.0022 μM. The threo isomer was at least 100-fold less active. The inhibition was specific for dTMP incorporation, and dGMP incorporation using (rC) n (dG) 12–18 as template/primer was not affected. The K m value for dTTP varied between 0.7 μM and 1.7 μM. Reverse transcriptase from nine HIV isolates were tested for inhibition by the erythro isomer and only slight differences in sensitivity were observed.