Pokholok D K, Gudima S O, Memelova L V, Esipov D S, Rechinskiĭ V O, Kochetkov S N
V.A. Engelgardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow.
Biokhimiia. 1996 Jan;61(1):142-51.
Prolonged treatment of AIDS patients with azidothymidine results in the development of resistance to the drug which correlates with the appearance of point mutations in the reverse transcriptase (RT) coding region within the HIV-1 pol gene. Kinetic studies of interactions of wild type RT and its mutants harbouring the above mutations with substrates and azidothymidine 5'-triphosphate (AZTTP) have been carried out. The complete mutant containing all the above described mutations possess the highest resistance on all the templates tested. Significant increases in resistance for mutants 67,70,215 and 67,215 on all the templates have also been observed. Inhibition of mutant enzymes by AZTTP depends on the template used.
用叠氮胸苷对艾滋病患者进行长期治疗会导致对该药物产生耐药性,这与HIV-1 pol基因逆转录酶(RT)编码区域内点突变的出现有关。已对野生型RT及其携带上述突变的突变体与底物和叠氮胸苷5'-三磷酸(AZTTP)之间的相互作用进行了动力学研究。包含所有上述突变的完整突变体在所有测试模板上具有最高的耐药性。在所有模板上也观察到突变体67、70、215以及67、215的耐药性显著增加。AZTTP对突变酶的抑制作用取决于所使用的模板。