INHIBITION OF VARICELLA-ZOSTER VIRUS-INDUCED DNA-POLYMERASE BY A NEW GUANOSINE ANALOG, 9-[4-HYDROXY-2-(HYDROXYMETHYL)BUTYL]GUANINE TRIPHOSPHATE
INHIBITION OF VARICELLA-ZOSTER VIRUS-INDUCED DNA-POLYMERASE BY A NEW GUANOSINE ANALOG, 9-[4-HYDROXY-2-(HYDROXYMETHYL)BUTYL]GUANINE TRIPHOSPHATE
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DOI：
10.1128/aac.32.8.1137
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发表时间：
1988-08-01
影响因子：
4.9
通讯作者：
WAHREN, B
中科院分区：
文献类型：
--
作者：
ABELE, G;ERIKSSON, B;WAHREN, B
研究了抗疱疹病毒无环鸟苷类似物9-[4-羟基-2-（羟甲基）丁基]鸟嘌呤（2mh - hbg）、9-（2-羟乙基氧甲基）鸟嘌呤（无环鸟苷[ACV]）和9-（3,4-二羟基丁基）鸟嘌呤（布昔洛韦）的三磷酸对部分纯化水痘-带状疱疹病毒（VZV） DNA聚合酶和细胞DNA聚合酶的影响。2HM-HBG的三磷酸竞争性地抑制由VZV DNA聚合酶催化的dGMP并入DNA。2hm - hbg -三磷酸（2HM-HBG-TP）对VZV DNA聚合酶dGTP结合位点的亲和力高于dGTP；dGTP和2HM-HBG-TP的表观Km和Ki值分别为0.64和0.034 .mu。M,分别。发现acv -三磷酸（ACV-TP）是VZV DNA聚合酶最有效的抑制剂。ACV-TP的直接抑制效果分别是2HM-HBG-TP和布昔洛韦-三磷酸的14倍和464倍。细胞（人胚胎肺成纤维细胞）DNA聚合酶。抑制作用与病毒聚合酶抑制作用的效比相关：2HM-HBG-TO的效比大于1000，与ACV-TP相似。
The triphosphates of the antiherpesvirus acyclic guanosine analogs 9-[4-hydroxy-2-(hydroxymethyl)butyl] guanine (2HM-HBG), 9-(2-hydroxyethyoxymethyl)guanine (acyclovir [ACV]), and 9-(3,4-dihydroxybutyl)guanine (buciclovir) were examined for their effects on partially purified varicella-zoster virus (VZV) DNA polymerase as well as cellular DNA polymerase .alpha.. The triphosphate of 2HM-HBG competitively inhibited the incorporation of dGMP into DNA catalyzed by the VZV DNA polymerase. 2HM-HBG-triphosphate (2HM-HBG-TP) had a higher affinity for the dGTP-binding site on the VZV DNA polymerase than did dGTP; apparent Km and Ki values of dGTP and 2HM-HBG-TP were 0.64 and 0.034 .mu.M, respectively. ACV-triphosphate (ACV-TP) was found to be the most potent inhibitor of VZV DNA polymerase. ACV-TP had a 14 and 464 times better direct inhibitory effect than 2HM-HBG-TP and buciclovir-triphosphate, respectively. The cellular (human embryonic lung fibroblast) DNA polymerase .alpha. inhibition was related to viral polymerase inhibition as efficacy ratios: 2HM-HBG-TO had a ratio of more than 1,000, which appeared to be similar to that of ACV-TP.