A guanine derivative with an acyclic side chain, 2-hydroxyethoxymethyl, at position 9 has potent antiviral activity [dose for 50% inhibition (ED(50)) = 0.1 muM] against herpes simplex virus type 1. This acyclic nucleoside analog, termed acycloguanosine, is converted to a monophosphate by a virus-specified pyrimidine deoxynucleoside (thymidine) kinase and is subsequently converted to acycloguanosine di- and triphosphates. In the uninfected host cell (Vero) these phosphorylations of acycloguanosine occur to a very limited extent. Acycloguanosine triphosphate inhibits herpes simplex virus DNA polymerase (DNA nucleotidyltransferase) 10-30 times more effectively than cellular (HeLa S3) DNA polymerase. These factors contribute to the drug's selectivity; inhibition of growth of the host cell requires a 3000-fold greater concentration of drug than does the inhibition of viral multiplication. There is, moreover, the strong possibility of chain termination of the viral DNA by incorporation of acycloguanosine. The identity of the kinase that phosphorylates acycloguanosine was determined after separation of the cellular and virus-specified thymidine kinase activities by affinity chromatography, by reversal studies with thymidine, and by the lack of monophosphate formation in a temperature-sensitive, thymidine kinase-deficient mutant of the KOS strain of herpes simplex virus type 1 (tsA1).

中文翻译：

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抗疱疹药9-（2-羟基乙氧基甲基）鸟嘌呤的选择性作用。

在第9位带有无环侧链2-羟基乙氧基甲基的鸟嘌呤衍生物对1型单纯疱疹病毒具有有效的抗病毒活性[抑制50％的剂量（ED（50））= 0.1μM]。这种无环核苷类似物，称为无环鸟苷通过病毒指定的嘧啶脱氧核苷（胸苷）激酶将α-磷酸酯转化为单磷酸酯，随后将其转化为无环鸟苷二磷酸酯和三磷酸鸟苷。在未感染的宿主细胞（Vero）中，无环鸟苷的这些磷酸化程度非常有限。无环鸟苷三磷酸对单纯疱疹病毒DNA聚合酶（DNA核苷酸转移酶）的抑制作用比细胞（HeLa S3）DNA聚合酶有效10-30倍。这些因素有助于药物的选择性。抑制宿主细胞生长所需的药物浓度要比抑制病毒繁殖高3000倍。此外，通过掺入无环鸟苷，很可能使病毒DNA终止链。通过亲和色谱法分离细胞和病毒特定的胸苷激酶活性，通过用胸苷逆转研究，以及在对温度敏感的胸苷激酶缺陷型突变体中缺乏单磷酸盐的形成，确定磷酸化无环鸟苷的激酶的身份。 1型单纯疱疹病毒（tsA1）的KOS株。