Thiol-mediated incorporation of radiolabel from 1-[14C]-methyl-4-phenyl-5-nitrosoimidazole into DNA. A model for the biological activity of 5-nitroimidazoles.
Thiol-mediated incorporation of radiolabel from 1-[14C]-methyl-4-phenyl-5-nitrosoimidazole into DNA. A model for the biological activity of 5-nitroimidazoles.
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硫醇介导将 1-[14C]-甲基-4-苯基-5-亚硝基咪唑放射性标记掺入 DNA。
DOI：
10.1016/0006-2952(89)90265-7
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发表时间：
1989
影响因子：
5.8
通讯作者：
Goldman,P
中科院分区：
文献类型：
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作者：
Ehlhardt,WJ;Goldman,P
1-甲基-4-苯基-5-亚硝基咪唑(5NO)具有与5-硝基咪唑的生物活性形式一致的性质，它被放射性标记(1-[14C]-甲基)并被证明与DNA结合，但速度太慢，无法解释其杀菌作用。然而，在细胞内存在谷胱甘肽等硫醇的生理浓度时，结合作用增加了2-3个数量级，这在数量上足以解释5NO的杀菌作用。聚[d(G-C)·d(G-C)J比聚[d(A-T)·d(A-T)J]的5NO结合更强，这表明反应物种与DNA上的亲核碱基结合，这一假设也得到了我们发现的5NO与苯胺之间形成加合物的硫醇依赖反应的支持。
1-Methyl-4-phenyl-5-nitrosoimidazole (5NO), which has properties consistent with the biologically active form of a 5-nitroimidazole, was radiolabeled (1-[14C]-methyl) and shown to bind to DNA, but at a rate too slow to account for its bactericidal effect. In the presence of physiological intracellular concentrations of such thiols as glutathione, however, binding was enhanced by 2–3 orders of magnitude, which is quantitatively sufficient to account for the bactericidal effect of 5NO. That 5NO binding was greater for poly[d(G-C) · d(G-C)J than for poly[d(A-T) · d(A-T)J suggests that the reactive species binds to nucleophilic bases on DNA, a suggestion which is also supported by our finding of a thiol-dependent reaction to form an adduct between 5NO and aniline.