AZT 5'-Cholinephosphate as an Anti-HIV Agent: The Study of Biochemical Properties and Metabolic Transformations Using Its super(32)P-Labelled Counterpart

Biochemical and metabolic transformations of 3'-azido-3'-deoxythymidine 5'-choline phosphate (1) were studied using its super(32)P-labelled counterpart for the evaluation of possible reasons for its enhanced anti-HIV activity. An effective synthesis of super(32)P-labelled 1 with a spe...

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Bibliographic Details
Published in:Nucleosides, nucleotides & nucleic acids nucleotides & nucleic acids, 2007-01, Vol.26 (1), p.23-36
Main Authors: Yanvarev, D V, Shirokova, E A, Astapova, M V, Skoblov, Y S
Format: Article
Language:English
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Summary:Biochemical and metabolic transformations of 3'-azido-3'-deoxythymidine 5'-choline phosphate (1) were studied using its super(32)P-labelled counterpart for the evaluation of possible reasons for its enhanced anti-HIV activity. An effective synthesis of super(32)P-labelled 1 with a specific activity >1,000 Ci/mmol was developed by esterification of super(32)P-phosphoric acid with choline in the presence of BrCN followed by the coupling of the resulting choline phosphate with 3'-azido-3'-deoxythymidine (AZT). Chemical and enzymatic stabilities of 1 as well as the dynamics of penetration through HL-60 cell membranes were studied at the concentrations comparable to its antiviral concentrations. The products of intracellular transformations of the studied nucleotide were identified.
ISSN:1525-7770
DOI:10.1080/15257770601052257