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

• Published in: Organic & biomolecular chemistry Vol. 8; no. 6; p. 1271
• Main Authors: Ahmadibeni, Y, Dash, C, Hanley, M J, Le Grice, S F J, Agarwal, H K, Parang, K
• Format: Journal Article
• Language: English
• Published: England 21-03-2010
• Subjects: HIV Reverse Transcriptase - antagonists & inhibitors; HIV Reverse Transcriptase - metabolism; HIV-1 - enzymology; Kinetics; Nucleotides - chemical synthesis; Nucleotides - chemistry; Nucleotides - pharmacology; Reverse Transcriptase Inhibitors - chemical synthesis; Reverse Transcriptase Inhibitors - chemistry; Reverse Transcriptase Inhibitors - pharmacology; Ribonuclease H - antagonists & inhibitors
• ISSN: 1477-0539
• DOI: 10.1039/b922846b

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.