无环鸟苷类似物作为水痘带状疱疹病毒胸苷激酶的底物
Acyclic guanosine analogs as substrates for varicella-zoster virus thymidine kinase.
作者信息
Karlström A R, Källander C F, Abele G, Larsson A
出版信息
Antimicrob Agents Chemother. 1986 Jan;29(1):171-4. doi: 10.1128/AAC.29.1.171.
Abstract
This study was performed to obtain information on the enzymatic background to the antiviral activity of acyclic guanosine analogs. Five acyclic guanosine analogs, the (R)- and (S)-enantiomers of 9-(3,4-dihydroxybutyl)guanine, 9-(4-hydroxybutyl)guanine, 9-[(2-hydroxyethoxy)methyl]guanine, and 9-[[2-hydroxy-1-(hydroxymethyl)ethoxy]methyl]guanine, were compared in enzyme kinetic experiments using purified varicella-zoster virus and human placenta mitochondrial thymidine kinase (TK). All analogs showed competitive patterns of inhibition in the phosphorylation of thymidine by varicella-zoster virus TK, but only low affinities and phosphorylation rates were observed. No affinity for the mitochondrial TK was observed for any of the analogs.
摘要
进行本研究以获取有关无环鸟苷类似物抗病毒活性的酶学背景信息。在使用纯化的水痘带状疱疹病毒和人胎盘线粒体胸苷激酶（TK）的酶动力学实验中，对5种无环鸟苷类似物，即9-(3,4-二羟基丁基)鸟嘌呤的(R)-和(S)-对映体、9-(4-羟基丁基)鸟嘌呤、9-[(2-羟基乙氧基)甲基]鸟嘌呤和9-[[2-羟基-1-(羟甲基)乙氧基]甲基]鸟嘌呤进行了比较。所有类似物在水痘带状疱疹病毒TK催化的胸苷磷酸化反应中均表现出竞争性抑制模式，但亲和力和磷酸化速率均较低。未观察到任何一种类似物对线粒体TK有亲和力。
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