Regulation of multi-factors (tail/loop/link/ions) for G-quadruplex enantioselectivity of Δ- and Λ- [Ru(bpy)2(dppz-idzo)]2+
Regulation of multi-factors (tail/loop/link/ions) for G-quadruplex enantioselectivity of Δ- and Λ- [Ru(bpy)2(dppz-idzo)]2+
复制标题
Delta- 和 Lambda- 的 G-四链体对映选择性的多因素（尾部/环/连接/离子）调节 [Ru(bpy)(2)(dppz-idzo)](2 )
DOI：
10.1039/c8dt00501j
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发表时间：
2018-04-21
影响因子：
4
通讯作者：
Shi, Shuo
中科院分区：
文献类型：
--
作者：
Hu, Xiaochun;Yang, Danjing;Shi, Shuo
DNA分子的手性识别非常重要，因为许多证据表明手性的转变和DNA的不同构象涉及一系列关键的生物事件。其中，基因组中G-四链体（GQ）的富集及其多重结构的探索引起了人们的极大兴趣。在此，我们比较了近 100 个具有可变长度或不同接头或不同环和突变离子浓度的 3' 尾序列的不同序列。所有序列均能够形成稳定的 GQ，与 Delta- 和 Lambda-[Ru(bpy)(2)(dppz-idzo)](2+) (Delta/Lambda-1) 结合后荧光信号增强。我们的结果表明，包括 3' 尾长度、接头、环长度和离子浓度在内的多种因素调节 GQ 的对映选择性。此外，分子对接模拟表明，GQ 的手性识别取决于结合位点。据我们所知，这是第一个关于手性 Ru 配合物 GQ 选择性多因素调节的系统研究。这些结果将为基因组GQ的对映选择性识别提供有用的参考，并可能促进针对GQ的手性抗癌药物的开发。
Chiral recognition of DNA molecules is important because much evidence has indicated that transformations of chirality and diverse conformations of DNA are involved in a series of key biological events. Among these, enrichment of G-quadruplexes (GQs) in the genome, and the exploration of their multiple structures, has aroused great interest. Herein, we compared nearly 100 different sequences with 3'-tail sequences of variable length or different linkers or diverse loops and mutative ionic concentrations. All sequences were capable of forming stable GQs, with fluorescence signal enhancement upon binding with Delta- and Lambda- [Ru(bpy)(2)(dppz-idzo)](2+) (Delta/Lambda-1). Our results show that multiple factors, including the 3'-tail length, linkers, loop length and ionic concentration, regulate the enantioselectivity of GQs. Furthermore, molecular docking simulations revealed that chiral recognition of GQs depends on the binding site. To the best of our knowledge, this is the first systematic study regarding the regulation of multi-factors for GQ selectivity of chiral Ru-complexes. These results will serve as a useful reference for enantioselective recognition of genomic GQs and may facilitate the development of chiral anticancer agents for targeting GQs.