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[单纯疱疹病毒1型DNA聚合酶的抑制分析]

[Inhibitory analysis of DNA polymerase of herpes simplex type 1].

作者信息

Kukhanova M K, Kuznetsova E V, Ias'ko M V, O'Hara B, Bekker J, Morin J, Gluzman Y a

出版信息

Mol Biol (Mosk). 1994 Jul-Aug;28(4):875-86.

PMID:7990816
Abstract

The inhibitory potency of new analogs of nucleoside 5'-triphosphates modified at the sugar residue and or alpha-phosphate against herpes simplex virus type 1 DNA polymerase has been evaluated in a cell-free system containing M13mp10 phage DNA and a synthetic primer. Triphosphates of new acyclic nucleosides [1-(5-hydroxy-2-cis-pentenyl)nucleosides] were the most effective inhibitors among 15 types of nucleoside 5'-triphosphates under investigation, being threefold less active than acyclovirtriphosphate. 5'-Phosphonylmethyl-2'-deoxythymidine beta, gamma-diphosphate proved to be a poor substrate for DNA polymerase. Compounds with other modifications at alpha-phosphate were inactive. Constants of hydrolysis rate of acyclonucleosides incorporated into the 3' end of primer were determined.

摘要

在含有M13mp10噬菌体DNA和合成引物的无细胞体系中,评估了在糖残基和/或α-磷酸处修饰的核苷5'-三磷酸新类似物对单纯疱疹病毒1型DNA聚合酶的抑制效力。新型无环核苷[1-(5-羟基-2-顺-戊烯基)核苷]的三磷酸酯是所研究的15种核苷5'-三磷酸酯中最有效的抑制剂,其活性比阿昔洛韦三磷酸酯低三倍。5'-膦酰甲基-2'-脱氧胸苷β,γ-二磷酸被证明是DNA聚合酶的不良底物。在α-磷酸处有其他修饰的化合物无活性。测定了掺入引物3'末端的无环核苷的水解速率常数。

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