Inhibition of the BamHI cleavage and unwinding of pBR322 deoxyribonucleic acid by the antitumor drug cis-dichlorodiammineplatinum(II).
Inhibition of the BamHI cleavage and unwinding of pBR322 deoxyribonucleic acid by the antitumor drug cis-dichlorodiammineplatinum(II).
复制标题
抗肿瘤药物顺式二氯二氨铂 (II) 对 pBR322 脱氧核糖核酸的 BamHI 裂解和解旋的抑制。
DOI：
10.1021/bi00516a012
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发表时间：
1981
期刊：
影响因子：
2.9
通讯作者：
Lippard,SJ
中科院分区：
文献类型：
--
作者：
Ushay,HM;Tullius,TD;Lippard,SJ
H. Michael Ushay、Thomas D. Tullius 和 Stephen J. Lippard* 摘要：抗肿瘤药物间二氯二氨铂 (II)(a's-DDP) 与 pBR322 DNA 结合，并抑制限制性内切酶 BamUl 将该环状 DNA 切割成线性形式。通过琼脂糖凝胶电泳监测铂与 DNA 的结合，并通过碳棒原子吸收光谱测量每个核苷酸 (rb) 的铂结合量。电泳迁移率变化反映了铂结合后 DNA 双链体的缩短和解旋，如之前观察到的顺式-和反式-DDP 与 pSMl DNA 的反应 [Cohen, G. L., Bauer, WR, Barton, J. K., & Lippard, S. J. (1979) Science (Washington, DC) 203, 1014-1016]，BamUl 核酸酶活性的抑制发生在非常低的结合水平并且在/-b= 0.045时完成。该值对应于所示酶识别序列±3个碱基对内的一个铂原子的结合
H. Michael Ushay, Thomas D. Tullius, and Stephen J. Lippard* abstract: The antitumor drug m-dichlorodiammineplatinum (II)(a's-DDP) binds to pBR322 DNA and inhibits the cleavage of this circular DNA into a linear form by the restriction endonuclease BamUl. The binding of platinum to DNA was monitored byagarose gel electrophoresis, and the amount of platinumbound per nucleotide (rb) was measured by carbon rod atomic absorption spectroscopy. Electrophoretic mobility changes reflect a shortening and unwinding of the DNA duplex upon platinum binding as observed previously for the reaction of cis-and frans-DDP with pSMl DNA [Cohen, G. L., Bauer, WR, Barton, J. K., & Lippard, S. J.(1979) Science {Washington, DC) 203, 1014-1016], The inhibition of BamUl nuclease activity occurs at very low binding levels and is complete at/-b= 0.045. This value corresponds to the binding of one platinum atom within±3 base pairs of the recognition sequence of the enzyme shown