感染单纯疱疹病毒的细胞中5-溴脱氧胞苷的磷酸化作用
Phosphorylation of 5-bromodeoxycytidine in cells infected with herpes simplex virus.
作者信息
Cooper G M
出版信息
Proc Natl Acad Sci U S A. 1973 Dec;70(12):3788-92. doi: 10.1073/pnas.70.12.3788.
Abstract
5-Bromodeoxycytidine is phosphorylated to 5-bromodeoxycytidine 5'-monophosphate in extracts of cells infected with herpes simplex virus but not in extracts of uninfected cells. The conversion of 5-bromodeoxycytidine to nucleotides and its utilization for DNA synthesis in uninfected cells occurs by deamination of 5-bromodeoxycytidine to 5-bromodeoxyuridine followed by phosphorylation of 5-bromodeoxyuridine to 5-bromodeoxyuridine 5'-monophosphate. In contrast, in cells infected with herpes simplex virus, 5-bromodeoxycytidine is phosphorylated directly to 5-bromodeoxycytidine 5'-monophosphate, which can then be deaminated to 5-bromodeoxyuridine 5'-monophosphate and incorporated into DNA. These results indicate a difference in the substrate specificity of nucleoside kinases induced by herpes simplex virus and the enzymes present in uninfected cells. It is suggested that this difference in substrate specificity between virus-induced and host-cell enzymes may allow selective chemotherapy of herpes simplex infections with 5-bromo- or 5-iododeoxycytidine.
摘要
5-溴脱氧胞苷在感染单纯疱疹病毒的细胞提取物中被磷酸化为5-溴脱氧胞苷5'-单磷酸，而在未感染细胞的提取物中则不会发生这种情况。在未感染的细胞中，5-溴脱氧胞苷转变为核苷酸并用于DNA合成的过程是，先将5-溴脱氧胞苷脱氨生成5-溴脱氧尿苷，然后将5-溴脱氧尿苷磷酸化为5-溴脱氧尿苷5'-单磷酸。相比之下，在感染单纯疱疹病毒的细胞中，5-溴脱氧胞苷直接被磷酸化为5-溴脱氧胞苷5'-单磷酸，然后可脱氨生成5-溴脱氧尿苷5'-单磷酸并掺入DNA中。这些结果表明单纯疱疹病毒诱导的核苷激酶与未感染细胞中存在的酶在底物特异性上存在差异。有人提出，病毒诱导的酶与宿主细胞酶之间在底物特异性上的这种差异可能使5-溴-或5-碘脱氧胞苷对单纯疱疹感染进行选择性化疗成为可能。
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