Second- and higher-order structural changes of DNA induced by antitumor-active tetrazolato-bridged dinuclear platinum(II) complexes with different types of 5-substituent
Second- and higher-order structural changes of DNA induced by antitumor-active tetrazolato-bridged dinuclear platinum(II) complexes with different types of 5-substituent
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DOI：
10.1016/j.jinorgbio.2013.05.004
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发表时间：
2013-10-01
影响因子：
3.9
通讯作者：
Komeda, Seiji
中科院分区：
文献类型：
--
作者：
Uemura, Masako;Yoshikawa, Yuko;Komeda, Seiji
在这里，我们使用圆二色性（CD）和荧光显微镜（FM）研究了一系列抗肿瘤活性的四唑拉托桥接双核铂（II）配合物，[{顺式- pt (NH3)(2)}(2)(mu-OH)(mu-5-R-tetrazolato-N2,N3)](n+) (R = CH3 (1), C6H3 (2), CH2COOCH2CH3 (3), CH2COO- (4), n = 2（1-3）或1(4))，它们是[{顺式- pt (NH3)(2)}(2)(mu-OH)(mu-tetrazolato-N2,N3)](2+) （5-H-Y）的衍生物。以阐明这些相互作用对DNA二级或高阶结构的影响，揭示作用机制。CD研究表明，3个带双正电荷的衍生物1-3改变了小牛胸腺DNA的二级结构，而唯一带单正电荷的复合物4几乎没有引起任何变化，这表明B-到c型构象的变化受到离子吸引力的影响。出乎意料的是，单分子FM观察显示，4在最低浓度下最有效地将T4 DNA的高阶结构改变为致密球状态，几乎与5-H-Y相当。这些相互矛盾的结果表明，二级结构变化不一定与高阶结构变化有关，非配位相互作用可以分为两种不同的相互作用：(1)离子吸引和(2)氢键和/或范德华接触。本文还讨论了扩散控制的非配位DNA相互作用与细胞毒性之间的关系。(C) 2013爱思唯尔公司版权所有。
Here, we used circular dichroism (CD) and fluorescence microscopy (FM) to examine the interactions of a series of antitumor-active tetrazolato-bridged dinuclear platinum(II) complexes, [{cis-Pt(NH3)(2)}(2)(mu-OH)(mu-5-R-tetrazolato-N2,N3)](n+) (R = CH3 (1), C6H3 (2), CH2COOCH2CH3 (3), CH2COO- (4), n = 2(1-3) or 1 (4)), which are derivatives of [{cis-Pt(NH3)(2)}(2)(mu-OH)(mu-tetrazolato-N2,N3)](2+) (5-H-Y), with DNA to elucidate the influence of these interactions on the secondary or higher-order structure of DNA and reveal the mechanism of action. The CD study showed that three derivatives, 1-3, with a double-positive charge altered the secondary structures of calf thymus DNA but that 4, the only complex with a single positive charge, induced almost no change, implying that the B- to C-form conformational change is influenced by ionic attraction. Unexpectedly, single-molecule observations with FM revealed that 4 changed the higher-order structure of T4 DNA into the compact-globule state most efficiently, at the lowest concentration, which was nearly equal to that of 5-H-Y. These contradictory results suggest that secondary structural changes are not necessarily linked to higher-order ones, and that the non-coordinative interaction could be divided into two distinct interactions: (1) ionic attraction and (2) hydrogen bonding and/or van der Waals contact. The relationship between diffusion-controlled non-coordinative DNA interactions and cytotoxicities is also discussed. (C) 2013 Elsevier Inc. All rights reserved.