模板结合n-甲基化atin-β-硫代氨基脲·铜复合物对大肠杆菌DNA聚合酶I的抑制作用

Peter Mikelens, Bruce Woodson, Warren Levinson
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引用次数: 4

摘要

脱氧核糖核酸聚合酶(脱氧核苷三磷酸:DNA脱氧核苷酸转移酶;50 μM n-甲基化atin-β-硫代氨基脲(M-IBT) + 50 μM CuSO4对大肠杆菌E.C 2.7.7.7)的抑制作用大于99%。单独添加50 μM - ibt可增强活性,而单独添加50 μM CuSO4可抑制40%的反应。抑制作用被竞争螯合剂乙二胺四乙酸酯逆转。一种相关的化合物,1-甲酰基异喹啉硫代氨基脲,在铜离子存在下也能抑制酶的活性。随着核酸添加量的增加,M-IBT + CuSO4对聚合酶的抑制作用得到缓解,而酶的添加量没有增加。这表明,DNA模板,而不是聚合酶,是M-IBT + CuSO4抑制的目标。劳斯肉瘤病毒(RSV) 70s RNA与完整病毒颗粒内形成的复合体结合,证明了核酸作为M-IBT + CuSO4复合体的生物学针对性。金属离子对这种药物作用的重要性得到了四乙酸乙二胺逆转结合能力的支持。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Inhibition of Escherichia coli DNA polymerase I by association of the template with an N-methylisatin-β-thiosemicarbazone·copper complex

The deoxyribonucleic acid polymerase I (deoxynucleoside triphosphate: DNA deoxynucleotidyl transferase; E.C 2.7.7.7) of Escherichia coli is inhibited more than 99% by 50 μM N-methylisatin-β-thiosemicarbazone (M-IBT) + 50 μM CuSO4. When added alone, 50 μM M-IBT enhanced activity, whereas 50 μM CuSO4 alone inhibits the reaction by 40%. Inhibition is reversed by the competing chelating agent ethylenediamine tetraacetate. A related compound, 1-formylisoquinoline thiosemicarbazone, also inhibits enzyme activity in the presence of cupric ions.

Polymerase inhibition by M-IBT + CuSO4 is relieved when increasing amounts of nucleic acid, but not increasing amounts of enzyme, are added. This suggests that the DNA template, not the polymerase, is the target of inhibition by M-IBT + CuSO4.

The biological pertinence of nucleic acid as a target for the M-IBT + CuSO4 complex is shown by the binding of Rous sarcoma virus (RSV) 70 S RNA to the complex formed within the intact virus particle. The importance of metal ions for this drug action is supported by the ability of ethylenediamine tetraacetate to reverse the binding.

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