4′C-Ethynyl-thymidine acts as a chain terminator during DNA-synthesis catalyzed by HIV-1 reverse transcriptase

Recently, 4′C-ethynyl nucleoside analogues have been identified as highly potent agents against HIV-1, including several multidrug-resistant strains. In contrast to most known nucleoside inhibitors 4′C-ethynyl nucleoside analogues possess a 3′-hydroxyl function. Here we show that the 5′O-triphosphate of 4′C-ethynyl thymidine gets readily incorporated into a nascent DNA strand by HIV-1 reverse transcriptase and significantly inhibits further post-incorporation chain extension by the enzyme.