INHIBITION OF RNA-DEPENDENT DNA POLYMERASE OF ROUS-SARCOMA VIRUS BY THIOSEMICARBAZONES AND SEVERAL CATIONS
INHIBITION OF RNA-DEPENDENT DNA POLYMERASE OF ROUS-SARCOMA VIRUS BY THIOSEMICARBAZONES AND SEVERAL CATIONS
复制标题
DOI：
10.1073/pnas.70.1.164
复制
发表时间：
1973-01-01
影响因子：
11.1
通讯作者：
BISHOP, JM
中科院分区：
文献类型：
--
作者：
LEVINSON, W;FARAS, A;BISHOP, JM
劳斯肉瘤病毒的rna依赖性DNA聚合酶被n -甲基isatin β-硫代氨基脲和硫代氨基脲抑制，但不被氨基脲抑制。当与病毒粒子接触时，这些抑制剂也灭活劳斯肉瘤病毒的转化能力。巯基供体，如2-巯基乙醇，可以防止这些影响。纯化后的聚合酶的rna定向活性比dna定向活性受到更大程度的抑制。Cu++和Hg++两种阳离子可以抑制rna依赖性DNA聚合酶，使病毒的转化能力失活。n -甲基isatin β-硫代氨基脲和Cu++之间存在协同作用，因为用低剂量的n -甲基isatin β-硫代氨基脲或Cu++治疗病毒效果很小；然而，当这两种化合物混合在一起时，会发生显著的失活。这一观察结果支持了一种假设，即硫代氨基脲的抗病毒作用是它们作为金属离子配体的能力的功能。Ag+、Co++、Zn++、Cd++和Ni++等阳离子对rna依赖性DNA聚合酶的失活作用显著，但对转化能力影响不大。鉴于这一结果，酶活性是转化所必需的这一结论仍有待商榷。
The RNA-dependent DNA polymerase of Rous sarcoma virus is inhibited byN-methyl isatin β-thiosemicarbazone and by thiosemicarbazide, but not by semicarbazide. These inhibitors also inactivate, upon contact with the virion, the transforming ability of Rous sarcoma virus. Sulfhydryl donors, such as 2-mercapto-ethanol, can prevent these effects. The RNA-directed activity of the purified polymerase is inhibited to a greater degree than is the DNA-directed activity.Two cations, Cu++and Hg++, can inhibit RNA-dependent DNA polymerase and inactivate the transforming ability of the virus. Synergism betweenN-methyl isatin β-thiosemicarbazone and Cu++occurs, since treatment of the virus with a low dose of eitherN-methyl isatin β-thiosemicarbazone or Cu++has little effect; however, when the two compounds are mixed together, significant inactivation occurs. This observation supports the hypothesis that the antiviral action of thiosemicarbazones is a function of their ability to act as a ligand for metallic ions.Several cations (Ag+, Co++, Zn++, Cd++, and Ni++) significantly inactivate the RNA-dependent DNA polymerase, but have little effect on the transforming ability. In view of this result, the conclusion that the enzyme activity is required for transformation remains open to question.