Disease relevance of Azidothymidine triphosphate

• Sequencing gel analysis demonstrated that the human immunodeficiency virus 1 reverse transcriptase preferentially incorporated N3dTTP into the T sites of the growing DNA strands and caused chain termination in a dose-dependent manner [1].
• Studies with reverse transcriptases from avian myeloblastosis virus and Moloney murine leukemia virus showed that N3dTTP was also efficiently incorporated into DNA by these enzymes and terminated DNA strand elongation [1].
• As expected from their mechanisms of action, pamidronate (but not PFA) synergistically inhibits HIV-1 RT in combination with AZT-triphosphate in the presence of PP(i) or ATP [2].
• The 5'-mono-, di- and triphosphate derivatives (N3dTMP, N3dTDP and N3dTTP respectively) of 3'-azidothymidine (N3dThd), a new drug for the treatment of the acquired immune deficiency syndrome (AIDS), were synthesized [3].

High impact information on Azidothymidine triphosphate

• To confirm the role of this polymerase in this process, we prepared cell extracts from the control and Pol beta overexpressing Chinese hamster ovary cell lines and tested in vitro their capacity to incorporate ddC-triphosphate and AZT-triphosphate into DNA [4].
• Like HIV-1(151M), HIV-1(151L) RT was found to have six- to eightfold resistance to AZT-triphosphate (TP), ddA-TP, and ddC-TP, indicating an MDNR phenotype [5].
• These results indicate that erythro-AZT-TP had an approximately 150-times-higher affinity to the enzyme than dTTP had and that the avian myeloblastosis virus reverse transcriptase had different binding sites for the two isomers [6].
• AZT-triphosphate is the active form of AZT, acting through inhibition of HIV reverse transcription [7].
• Alpha, beta- and beta, gamma-methylene 5'-phosphonate derivatives of 3'-azido-2',3'-dideoxythymidine-5'-triphosphate. Correlation between affinity for reverse transcriptase, susceptibility to hydrolysis by phosphodiesterases and anti-retrovirus activity [8].

Chemical compound and disease context of Azidothymidine triphosphate

• The action of 3'-azido-3'-deoxythymidine 5'-triphosphate (N3dTTP) on DNA strand elongation catalyzed by human immunodeficiency virus type 1 reverse transcriptase was evaluated in comparison with human DNA polymerase alpha and proliferating cell nuclear antigen-independent DNA polymerase delta [1].

Biological context of Azidothymidine triphosphate

• In contrast, the AZT-selected substitutions studied did not cause as great a change in the IC50 of AZT-triphosphate (AZT-TP) for polymerase as they did in the IC50 of AZT for mutant virus [9].

Anatomical context of Azidothymidine triphosphate

• Hybrid polymer nanocapsules enhance in vitro delivery of azidothymidine-triphosphate to macrophages [10].

Gene context of Azidothymidine triphosphate

• DNA polymerase beta is partially affected by N3dTTP (ID50 = 31 microM) and by the other analogues (ID50 = 1-2.2 microM) [11].

References