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.
Summerer
Daniel
D
Fachbereich Chemie, Universität Konstanz, Universitätsstrasse 10, D-78457 Konstanz, Germany.
Marx
Andreas
A
D002384:Catalysis / Q000187:drug effects; D054303:HIV Reverse Transcriptase / Q000378:metabolism*; D007700:Kinetics; D014176:Protein Biosynthesis / Q000187:drug effects*; D018894:Reverse Transcriptase Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013936:Thymidine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology*
C501165:4'C-ethynyl-thymidine; D018894:Reverse Transcriptase Inhibitors; D054303:HIV Reverse Transcriptase; D013936:Thymidine