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Synthesis of nucleoside 5'-O-alpha,beta-methylene-beta-triphosphates and evaluation of their potency towards inhibition of HIV-1 reverse transcriptase.

ABSTRACT: A polymer-bound alpha,beta-methylene-beta-triphosphitylating reagent was synthesized and subjected to reactions with unprotected nucleosides, followed by oxidation, deprotection of cyanoethoxy groups, and acidic cleavage to afford nucleoside 5'-O-alpha,beta-methylene-beta-triphosphates. Among all the compounds, cytidine 5'-O-alpha,beta-methylene-beta-triphosphate inhibited RNase H activity of HIV-1 reverse transcriptase with a K(i) value of 225 microM.

SUBMITTER: Ahmadibeni Y

PROVIDER: S-EPMC2928660 | biostudies-literature | 2010 Mar

REPOSITORIES: biostudies-literature

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Synthesis of nucleoside 5'-O-alpha,beta-methylene-beta-triphosphates and evaluation of their potency towards inhibition of HIV-1 reverse transcriptase.

Ahmadibeni Y Y Dash C C Hanley M J MJ Le Grice S F J SF Agarwal H K HK Parang K K

Organic & biomolecular chemistry 20100113 6

A polymer-bound alpha,beta-methylene-beta-triphosphitylating reagent was synthesized and subjected to reactions with unprotected nucleosides, followed by oxidation, deprotection of cyanoethoxy groups, and acidic cleavage to afford nucleoside 5'-O-alpha,beta-methylene-beta-triphosphates. Among all the compounds, cytidine 5'-O-alpha,beta-methylene-beta-triphosphate inhibited RNase H activity of HIV-1 reverse transcriptase with a K(i) value of 225 microM. ...[more]

PMID: 20204192

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