[Reactions of 5'-H-phosphonates, 5'-F-phosphates, and 5'-phosphates of modified thymidines in human blood plasma].
Mechanisms and rates of hydrolytic dephosphorylation of 5'-hydrogen phosphonates, 5'-fluorophosphates, and 5'-phosphates of 3'-azido-3'-deoxythymidine, 3'-fluoro-3'-deoxythymidine, and thymidine in human blood serum were investigated. 5'-Hydrogen phosphonates of 3'-substituted thymidines are dephosphorylated 50-100 times slower than the corresponding 5'-phosphates. 5'-fluorophosphates of 3'-substituted thymidines are dephosphorylated 2 times slower than corresponding 5'-phosphates; first, substituted thymidine 5'-phosphates are formed, which are later dephosphorylated into substituted thymidines. These data illustrate probable molecular mechanisms of anti-HIV action of such nucleotides. 5'-hydrogen phosphonates of thymidines can serve as depot forms of corresponding thymidines, but other metabolic pathways are not excluded. Thymidine 5'-fluorophosphates can serve as depot-forms of both thymidines and their phosphates. Their fate in cells depends probably on their diffusion and on the activities of dephosphorylating and phosphorylating enzymes.
Kuznetsova
E V
EV
Kukhanova
M K
MK
Arzumanov
A A
AA
Kraevskiĭ
A A
AA
D005461:Fluorine / Q000737:chemistry; D006801:Humans; D006859:Hydrogen / Q000737:chemistry; D006868:Hydrolysis; D007700:Kinetics; D063065:Organophosphonates / Q000097:blood / Q000737:chemistry*; D010710:Phosphates / Q000097:blood / Q000737:chemistry*; D010766:Phosphorylation; D013936:Thymidine / Q000097:blood / Q000737:chemistry*
D063065:Organophosphonates; D010710:Phosphates; D005461:Fluorine; D006859:Hydrogen; D013936:Thymidine
Reaktsii 5'-H-fosfonataov, 5'-F-fosfatov i 5'-fosfatov modifitsirovannykh timidinov v plazme krovi cheloveka.