Abstract
Biochemical and metabolic transformations of 3′-azido-3′-deoxythymidine 5′-choline phosphate (1) were studied using its 32P-labelled counterpart for the evaluation of possible reasons for its enhanced anti-HIV activity. An effective synthesis of 32P-labelled 1 with a specific activity >1,000 Ci/mmol was developed by esterification of 32P-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.
The work was supported by the Russian Foundation for Basic Research, projects 04-03-32481, 05-04-49500 and 04-04-49617; and the program of Presidium of Russian Academy of Sciences “Molecular and Cellular Biology.”