Siegel S A, Otto M J, De Clercq E, Prusoff W H
Antimicrob Agents Chemother. 1984 May;25(5):566-70. doi: 10.1128/AAC.25.5.566.
The antiherpesvirus agent (E)-5-(2-bromovinyl)-2'-deoxyuridine caused marked alterations in the synthesis and processing of several herpes simplex virus type 1 (HSV-1)-infected-cell polypeptides. Analogous to other thymidine analogs, there was a dose-dependent decrease in several beta and gamma polypeptides and an accumulation of HSV-1 thymidine kinase. In contrast to the action of other thymidine analogs, there were alterations in alpha polypeptides, including an increase in the synthesis and phosphorylation of infected-cell polypeptide 4b and a decrease in the synthesis of infected-cell polypeptide 27. The phosphorylation of several other HSV-1 phosphoproteins was mildly inhibited. (E)-5-(2-Bromovinyl)-2'-deoxyuridine inhibited the glycosylation of the major HSV-1 glycoproteins, and this activity appeared to be independent of the incorporation of the drug into the viral DNA. Thus, the alterations in HSV-1 polypeptide expression appear to be due to the presence of the drug in a low-molecular-weight form as well as its presence in the viral DNA. This suggests that this analog or a phosphorylated derivative might act as an inhibitor of an enzyme(s) responsible for posttranslational modification of polypeptides.
抗疱疹病毒药物(E)-5-(2-溴乙烯基)-2'-脱氧尿苷导致单纯疱疹病毒1型(HSV-1)感染细胞的几种多肽的合成和加工发生显著改变。与其他胸苷类似物相似,几种β和γ多肽呈剂量依赖性减少,HSV-1胸苷激酶积累。与其他胸苷类似物的作用相反,α多肽发生改变,包括感染细胞多肽4b的合成和磷酸化增加以及感染细胞多肽27的合成减少。其他几种HSV-1磷蛋白的磷酸化受到轻度抑制。(E)-5-(2-溴乙烯基)-2'-脱氧尿苷抑制HSV-1主要糖蛋白的糖基化,并且这种活性似乎与药物掺入病毒DNA无关。因此,HSV-1多肽表达的改变似乎是由于药物以低分子量形式存在以及其在病毒DNA中的存在。这表明该类似物或磷酸化衍生物可能作为负责多肽翻译后修饰的一种或多种酶的抑制剂。