Otto M J, Prusoff W H
Antiviral Res. 1984 Oct;4(5):271-80. doi: 10.1016/0166-3542(84)90032-9.
As part of our studies on the molecular basis for the antiherpes activity of 5'-AdThd (5'-amino-5'-deoxythymidine), a study of the HSV-1 DNA synthesized in infected Vero cells exposed to 5'-AdThd was undertaken. Unlike many other antiviral nucleoside analogs, 5'-AdThd did not inhibit HSV-1 DNA synthesis. Analysis of the DNA synthesized in the presence of [14C]5'-AdThd revealed that the analog was incorporated into the viral DNA in a dose-dependent manner and that the degree of incorporation correlated with the antiviral activity as measured by yield reduction assays. Analysis of the 5'-AdThd substituted DNA by centrifugation in neutral and alkaline sucrose gradients revealed no double-stranded breaks but an increase in single-stranded breaks, at very high concentrations of the analog. Analysis of HSV-1-specific RNAs revealed a shift from poly(A+) to poly(A-) RNA. The degree of this shift paralleled the substitution of 5'-AdThd for thymidine in the HSV-1 DNA.
作为我们对5'-AdThd（5'-氨基-5'-脱氧胸苷）抗疱疹活性分子基础研究的一部分，我们对在暴露于5'-AdThd的受感染Vero细胞中合成的单纯疱疹病毒1型（HSV-1）DNA进行了研究。与许多其他抗病毒核苷类似物不同，5'-AdThd不抑制HSV-1 DNA合成。对在[14C]5'-AdThd存在下合成的DNA的分析表明，该类似物以剂量依赖的方式掺入病毒DNA中，并且掺入程度与通过产量降低试验测量的抗病毒活性相关。通过在中性和碱性蔗糖梯度中离心分析5'-AdThd取代的DNA，结果显示在该类似物的非常高浓度下没有双链断裂，但单链断裂增加。对HSV-1特异性RNA的分析显示从多聚腺苷酸（A+）RNA向多聚腺苷酸（A-）RNA的转变。这种转变的程度与HSV-1 DNA中5'-AdThd取代胸苷的情况平行。
