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儿茶素衍生物对人类免疫缺陷病毒逆转录酶和DNA聚合酶活性的抑制作用

[The inhibitory effects of catechin derivatives on the activities of human immunodeficiency virus reverse transcriptase and DNA polymerases].

作者信息

Tao P

机构信息

Institute of Medical Biotechnology, Beijing.

出版信息

Zhongguo Yi Xue Ke Xue Yuan Xue Bao. 1992 Oct;14(5):334-8.

PMID:1284389
Abstract

Catechin derivatives including (-)-epicatechin gallate (ECG), (-)-epigallocatechin gallate (EGCG), (-)-epigallocatechin (EGC) and green tea extract (GTE) were found to inhibit the activities of cloned human immunodeficiency virus type 1 reverse transcriptase (HIV-1 RT), duck hepatitis B virus replication complexes reverse transcriptase (DHBV RCs RT), herpes simplex virus 1 DNA polymerase (HSV-1 DNAP) and cow thymus DNA polymerase alpha (CT DNAP alpha). EGCG and ECG were shown to be very potent inhibitors of HIV-1 RT. According to the IC50 values for HIV-1 RT, these compounds can be ordered as EGCG 0.0066 mumol/L > ECG 0.084 mumol/L > GTE 0.1 microgram/ml > EGC 7.2 mumol/L. DHBV RCs RT was the least sensitive to these compounds. Kinetic study showed that EGCG exerts a mixed inhibition with respect to external template inducer poly (rA).oligo (dT) 12-18 and a noncompetitive inhibition with respect to substrate dTTP for HIV-1 RT. Bovine serum albumin significantly reduced the inhibitory effects of catechin analogues and GTE on HIV-1 RT. In tissue culture GTE inhibited the cytopathic effect of coxsackie B3 virus, but did not inhibit the cytopathic effects of HSV-1, HSV-2, influenza A or influenza B viruses.

摘要

儿茶素衍生物,包括(-)-表儿茶素没食子酸酯(ECG)、(-)-表没食子儿茶素没食子酸酯(EGCG)、(-)-表没食子儿茶素(EGC)和绿茶提取物(GTE),被发现可抑制克隆的人类免疫缺陷病毒1型逆转录酶(HIV-1 RT)、鸭乙型肝炎病毒复制复合物逆转录酶(DHBV RCs RT)、单纯疱疹病毒1型DNA聚合酶(HSV-1 DNAP)和牛胸腺DNA聚合酶α(CT DNAPα)的活性。EGCG和ECG被证明是HIV-1 RT的非常有效的抑制剂。根据HIV-1 RT的IC50值,这些化合物的排序为:EGCG 0.0066 μmol/L > ECG 0.084 μmol/L > GTE 0.1 μg/ml > EGC 7.2 μmol/L。DHBV RCs RT对这些化合物最不敏感。动力学研究表明,EGCG对外部模板诱导剂聚(rA)·寡聚(dT)12-18表现出混合抑制作用,对HIV-1 RT的底物dTTP表现出非竞争性抑制作用。牛血清白蛋白显著降低了儿茶素类似物和GTE对HIV-1 RT的抑制作用。在组织培养中,GTE抑制柯萨奇B3病毒的细胞病变效应,但不抑制HSV-1、HSV-2、甲型流感或乙型流感病毒的细胞病变效应。

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