Hao Z, Cooney D A, Farquhar D, Perno C F, Zhang K, Masood R, Wilson Y, Hartman N R, Balzarini J, Johns D G
Division of Cancer Treatment, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892.
Mol Pharmacol. 1990 Feb;37(2):157-63.
2',3'-Dideoxyuridine (ddUrd) exhibits poor if any anti-human immunodeficiency virus (HIV) activity in ATH8 and MT-4 cells. This is in agreement with the failure of ddUrd to be efficiently anabolized intracellularly to its 5'-triphosphate metabolite. However, 2',3'-dideoxyuridine-5'-triphosphate (ddUTP) proved to be a potent and selective inhibitor of the reverse transcriptase of HIV (Ki, 0.05 microM) and avian myeloblastosis virus (Ki, 1.0 microM). Bacterial DNA polymerase I, mammalian DNA polymerase alpha, terminal deoxyribonucleotidyl transferase, and Moloney murine leukemia virus reverse transcriptase were resistant to ddUTP. ddUTP is incorporated into the growing DNA chain principally at dTTP sites and inhibits further elongation. The potential of ddUTP as an anti-HIV therapeutic agent merits further investigation. However, to achieve this goal, it will be necessary to resort to techniques capable of delivering preformed phosphorylated ddUrd to the susceptible cells.
2',3'-二脱氧尿苷（ddUrd）在ATH8细胞和MT - 4细胞中即便有抗人类免疫缺陷病毒（HIV）的活性也很微弱。这与ddUrd不能在细胞内有效地合成其5'-三磷酸代谢物的情况相符。然而，2',3'-二脱氧尿苷-5'-三磷酸（ddUTP）被证明是HIV逆转录酶（Ki，0.05微摩尔）和禽成髓细胞瘤病毒逆转录酶（Ki，1.0微摩尔）的一种强效且选择性的抑制剂。细菌DNA聚合酶I、哺乳动物DNA聚合酶α、末端脱氧核苷酸转移酶以及莫洛尼鼠白血病病毒逆转录酶对ddUTP具有抗性。ddUTP主要在dTTP位点掺入正在增长的DNA链中并抑制进一步延伸。ddUTP作为一种抗HIV治疗剂的潜力值得进一步研究。然而，要实现这一目标，将有必要采用能够将预先形成的磷酸化ddUrd递送至易感细胞的技术。
