Open AccessSynthesis of nucleoside 5′-O-α,β-methylene-β-triphosphates and evaluation of their potency towards inhibition of HIV-1 reverse transcriptase
Author(s) -
Yousef Ahmadibeni,
Chandravanu Dash,
Michael Hanley,
Stuart F. J. Le Grice,
Hitesh K. Agarwal,
Keykavous Parang
Publication year - 2010
Publication title -
organic and biomolecular chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.923
H-Index - 146
eISSN - 1477-0539
pISSN - 1477-0520
DOI - 10.1039/b922846b
Subject(s) - chemistry , methylene , reverse transcriptase , nucleoside , reagent , cytidine , rnase h , nucleotide , zidovudine , nucleoside analogue , nucleoside triphosphate , human immunodeficiency virus (hiv) , rnase p , nucleoside reverse transcriptase inhibitor , enzyme , stereochemistry , biochemistry , medicinal chemistry , organic chemistry , rna , virology , gene , viral disease , biology
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.