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

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 a...

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Veröffentlicht in:	Organic & biomolecular chemistry 2010-03, Vol.8 (6), p.1271-1274
Hauptverfasser:	Ahmadibeni, Y, Dash, C, Hanley, M J, Le Grice, S F J, Agarwal, H K, Parang, K
Format:	Artikel
Sprache:	eng
Schlagworte:	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
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Beschreibung
Zusammenfassung:	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.
ISSN:	1477-0520 1477-0539
DOI:	10.1039/b922846b