AZT 5'-Cholinephosphate as an anti-HIV agent: the study of biochemical properties and metabolic transformations using its 32P-labelled counterpart.
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.
Yanvarev
Dmitry V
DV
Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russian Federation. vsupport@bk.ru
Shirokova
Elena A
EA
Astapova
Maria V
MV
Skoblov
Yury S
YS
D019380:Anti-HIV Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism*; D001692:Biological Transport; D001711:Biotransformation; D002457:Cell Extracts / Q000737:chemistry; D054306:Dideoxynucleotides; D004798:Enzymes / Q000737:chemistry; D018922:HL-60 Cells; D006801:Humans; D013938:Thymidine Monophosphate / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism; D015215:Zidovudine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism
C518807:3'-azido-3'-deoxythymidine 5'-choline phosphate; D019380:Anti-HIV Agents; D002457:Cell Extracts; D054306:Dideoxynucleotides; D004798:Enzymes; D013938:Thymidine Monophosphate; D015215:Zidovudine