21-钨-9-锑酸铵（HPA23）对各种哺乳动物DNA聚合酶活性的差异抑制作用

Differential inhibition of various mammalian DNA polymerase activities by ammonium 21-tungsto-9-antimoniate (HPA23).

作者信息

Ono K, Nakane H, Barré-Sinoussi F, Chermann J C

机构信息

Laboratory of Viral Oncology, Aichi Cancer Center Research Institute, Nagoya, Japan.

出版信息

Eur J Biochem. 1988 Sep 15;176(2):305-10. doi: 10.1111/j.1432-1033.1988.tb14282.x.

DOI:10.1111/j.1432-1033.1988.tb14282.x

PMID:2458259

Abstract

The 21-tungsto-9-antimoniate ammonium salt (HPA23), known as an antiviral agent, has been shown to be a potent inhibitor of both human and murine DNA polymerase alpha and murine DNA polymerase gamma. HPA23 inhibited the activity of DNA polymerase alpha in noncompetitive fashion with respect to either deoxynucleotide substrate or nucleic acid template.primer. The Ki of murine DNA polymerase alpha for HPA23 was determined to be 24 nM. The activity of mouse DNA polymerase gamma also was strongly inhibited by HPA23 (Ki, 20 nM), and the mode of inhibition was competitive with respect to the template.primer, (rA)n.(dT)12-18, and noncompetitive to substrate, dTTP. DNA polymerase beta and terminal deoxynucleotidyltransferase, however, were relatively resistant to inhibition by HPA23. The observed inhibitions by HPA23 seem to be closely related to the polyanionic property of this drug.

摘要

21-钨-9-锑酸铵盐（HPA23）作为一种抗病毒剂，已被证明是人和鼠DNA聚合酶α以及鼠DNA聚合酶γ的有效抑制剂。HPA23以非竞争性方式抑制DNA聚合酶α的活性，无论是对于脱氧核苷酸底物还是核酸模板-引物。鼠DNA聚合酶α对HPA23的Ki值测定为24 nM。小鼠DNA聚合酶γ的活性也受到HPA23的强烈抑制（Ki，20 nM），抑制模式对于模板-引物(rA)n.(dT)12-18是竞争性的，而对于底物dTTP是非竞争性的。然而，DNA聚合酶β和末端脱氧核苷酸转移酶对HPA23的抑制相对具有抗性。观察到的HPA23的抑制作用似乎与该药物的聚阴离子特性密切相关。