"Head-to-head" double-hamburger-like structure of di-ruthenated d(GpG) adducts of monofunctional Ru-arene anticancer complexes
"Head-to-head" double-hamburger-like structure of di-ruthenated d(GpG) adducts of monofunctional Ru-arene anticancer complexes
复制标题
单功能Ru-芳烃抗癌复合物的二钌d(GpG)加合物的“头对头”双汉堡样结构
DOI：
10.1039/c6dt03356c
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发表时间：
2016
影响因子：
4
通讯作者：
Sadler Peter J.
中科院分区：
文献类型：
--
作者：
Liu Hong-Ke;Kostrhunova Hana;Habtemariam Abraha;Kong Yaqiong;Deeth Robert J.;Brabec Viktor;Sadler Peter J.
DNA中的鸟嘌呤碱基是某些Ru-芳烃抗癌配合物的靶标。研究了新型双亚甲酸d(Gpg)加合物Ru2-Gpg(其中Ru={(η6-联苯)-Ru(En)}2+(1‘))在水溶液中的结构。2D核磁共振结果表明存在两个构象，模拟研究支持这一结果。主要构象I是一种新颖的双汉堡结构，具有“头对头”(HH)碱基排列，涉及相邻芳环之间的疏水相互作用，这是通过弱相互作用构建HH d(GPG)加合物的第一个例子。因此，与顺铂形成的铂-d(GPG)加合物相比，存在显着差异。RU2-GPG的主要构象I没有明显的刚性弯曲，次要构象II具有背靠背的结构，两个鸟嘌呤碱基相互翻转。含有中心TGGT序列的19-23碱基寡聚脱氧核糖核苷酸没有定向弯曲，只有轻微扭曲的双链，这与构象I的核磁共振数据一致。本文结合这些金属络合物的生物活性，讨论了双硫化或交联化的d(GPG)残基的结构异同。
Guanine bases in DNA are targets for some Ru–arene anticancer complexes. We have investigated the structure of the novel di-ruthenated d(GpG) adduct Ru2-GpG (where Ru = {(η6-biphenyl)-Ru(en)}2+ (1′)) in aqueous solution. 2D NMR results indicate that there are two conformers, supported by modeling studies. The major conformer I is a novel double-hamburger-like structure with a “head-to-head” (HH) base arrangement involving hydrophobic interactions between neighboring arene rings, the first example of a HH d(GpG) adduct constructed by weak interactions. Hence there are significant differences compared to Pt-d(GpG) adducts formed by cisplatin. There is no obviously rigid bending for the major conformer I. The minor conformer II of Ru2-GpG has a back-to-back structure, with two ruthenated guanine bases flipped away from each other. 19-23 base-pair oligodeoxyribonucleotides containing central TGGT sequences di-ruthenated by 1 show no directional bending, only slightly distorted di-ruthenated duplexes, consistent with the NMR data for conformer I. The structural differences and similarities of d(GpG) residues which are di-ruthenated or cross-linked by platination are discussed in the context of the biological activity of these metal complexes.