DNA binding, cleavage, and cytotoxic activity of the preorganized dinuclear zinc(II) complex of triazacyclononane derivatives
DNA binding, cleavage, and cytotoxic activity of the preorganized dinuclear zinc(II) complex of triazacyclononane derivatives
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三氮杂环壬烷衍生物预组织双核锌 (II) 复合物的 DNA 结合、裂解和细胞毒活性
DOI：
10.1021/bc700322w
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发表时间：
2008-02-01
影响因子：
4.7
通讯作者：
Xu, Qiang
中科院分区：
文献类型：
--
作者：
Sheng, Xin;Guo, Xun;Xu, Qiang
用改进的方法制备了人工核酸酶2，6-bis(1-methyl-1，4，7-triazacyclonon-1-yl)pyridine-1的裂隙双核锌(II)络合物。用荧光、圆二色谱等光谱技术研究了1，2-[1，4，7-三氮杂环烷(TACN)]及其锌(H)配合物与小牛胸腺DNA的相互作用。结果表明，这些化合物与DNA的亲和力大小顺序为：锌-2(II)-1>；锌-II-2>；1-GT；2.锌-2(II)-1和锌-II-2的结合常数分别为3.57×10(6)和1.43×10(5)M-1。用琼脂糖凝胶电泳法测定了双核锌-2(II)-1配合物对PUC19DNA的切割活性。在生理条件下，锌-L配合物促进DNA切割的动力学数据给出了观察到的速率常数(k(Obs))为0。136h(-1)，与非催化超螺旋DNA相比，速度提高了10(7)倍。双核锌-2(II)-1配合物与单核1.4，7-三氮杂环烷锌(II)配合物的比较表明，锌-2(II)-1配合物的DNA切割加速是由于两个近邻的锌(II)阳离子中心的协同催化作用。提出了裂解过程的水解机理，并对其抗肿瘤活性进行了初步研究。
A preorganized cleft dinuclear zinc(II) complex of 2,6-bis(1-methyl-1,4,7-triazacyclonon-1-yl)pyridine 1 as an artificial nuclease was prepared via an improved method. The interactions of 1, 2 [1,4,7-triazacyclononane (TACN)], and their zinc(H) complexes with calf thymus DNA were studied by spectroscopic techniques, including fluorescence and CD spectroscopy. The results indicate that the DNA binding affinities of these compounds are in the following order: Zn-2(II)-1 > Zn-II-2 > 1 > 2. The binding constants of the Zn-2(II)-1 and Zn-II-2 complexes are 3.57 x 10(6) and 1.43 x 10(5) M-1, respectively. Agarose gel electrophoresis was used to assess the plasmid pUC 19 DNA cleavage activities in the presence of the dinuclear Zn-2(II)-1 complex, which exhibits powerful DNA cleavage efficiency, Kinetic data for DNA cleavage promoted by the Zn",)-l complex under physiological conditions give the observed rate constant (k(obs)) of 0. 136 h(-1), which shows an 10(7)-fold rate acceleration over uncatalyzed supercoiled DNA. The comparison of the dinuclear Zn-2(II)-1 complex with the mononuclear zinc(II) complex of 1.4,7-triazacyclononane indicates that the DNA cleavage acceleration promoted by the Zn-2(II)-1 complex is due to the efficient cooperative catalysis of the two proximate zinc(II) cation centers. A hydrolytic mechanism of the cleavage process was suggested, and a preliminary study of the antitumor activity was also conducted.