Regulation of multi-factors (tail/loop/link/ions) for G-quadruplex enantioselectivity of Δ- and Λ- [Ru(bpy)2(dppz-idzo)]2+†,Dalton Transactions

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Regulation of multi-factors (tail/loop/link/ions) for G-quadruplex enantioselectivity of Δ- and Λ- [Ru(bpy)2(dppz-idzo)]2+†
Dalton Transactions ( IF 3.5 ) Pub Date : 2018-03-16 00:00:00 , DOI: 10.1039/c8dt00501j
Xiaochun Hu _{1,

2,

3,

4,

5} , Danjing Yang _{1,

2,

3,

4,

5} , Tianming Yao _{1,

2,

3,

4,

5} , Ruru Gao _{1,

2,

3,

4,

5} , Maierhaba Wumaier _{1,

2,

3,

4,

5} , Shuo Shi _{1,

2,

3,

4,

5}

Affiliation

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 Δ- and Λ- [Ru(bpy)₂(dppz-idzo)]²⁺ (Δ/Λ-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.

中文翻译：

G-四元对映体对Δ-和Λ- [Ru（bpy）₂（dppz-idzo）] 2 ⁺†的多因素（尾/环/链/离子）的调节

DNA分子的手性识别很重要，因为许多证据表明，手性的转化和DNA的各种构象涉及一系列关键的生物学事件。其中，基因组中G-四链体（GQs）的富集及其多种结构的探索引起了人们的极大兴趣。在本文中，我们将近100个不同序列与可变长度或不同接头或不同环和突变离子浓度的3'尾序列进行了比较。所有序列均能够形成稳定的GQ，与Δ-和Λ- [Ru（bpy）₂（dppz-idzo）] ²⁺（Δ/Λ-1结合后，荧光信号增强）。我们的结果表明，多个因素，包括3'尾长度，连接子，环长度和离子浓度，调节GQs的对映选择性。此外，分子对接模拟显示手性识别GQs取决于结合位点。据我们所知，这是第一个关于多因素调控手性Ru-配合物GQ选择性的系统研究。这些结果将为对基因组GQ的对映选择性识别提供有用的参考，并可能有助于开发靶向GQ的手性抗癌药。

更新日期：2018-03-16

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