G-quadruplex and duplex DNA binding studies of novel Ruthenium(II) complexes containing ascididemin ligands
G-quadruplex and duplex DNA binding studies of novel Ruthenium(II) complexes containing ascididemin ligands
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含有海鞘胺配体的新型钌 (II) 配合物的 G-四链体和双链体 DNA 结合研究
DOI：
10.1016/j.jinorgbio.2019.03.021
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发表时间：
2019-07-01
影响因子：
3.9
通讯作者：
Shi, Shuo
中科院分区：
文献类型：
--
作者：
Wumaier, Maierhaba;Shi, Jing-Jing;Shi, Shuo
本文合成并表征了三种以ascididemin（ASC）为主要配体的新型钌（II）聚吡啶配合物。通过一系列光谱分析，比较研究了它们与不同 G-四链体（Htelo、c-myc 和 c-kit）（Htelo：人端粒 DNA、c-myc：细胞骨髓细胞瘤病病毒癌基因、c-kit：癌基因 c-kit 启动子序列）和双链体 (ds26) DNA 序列与游离配体 ASC 的相互作用。 技术包括UV-vis（紫外-可见）光谱、FID（荧光嵌入剂置换）测定和FRET（荧光共振能量转移）熔解测定。还进行了分子对接研究以支持化合物与 G-四链体 DNA 的结合模式。结果表明[Ru(bpy)(2)ASC]中心点(PF6)(2) (1)、[Ru(phen)(2)ASC]中心点(PF6)(2) (2)、[Ru(tatp)(2)ASC]中心点(PF6)(2) (3) (bpy 2,2'-联吡啶, = phen = 1,10-菲咯啉, tatp = 1,4,8,9-四氮杂苯并菲)和ASC可以有效结合G-四链体和双链体DNA，稳定能力的顺序为3>2>1>ASC。复合物3被确定为最有希望进行进一步体外研究和潜在抗癌药物的候选药物。
In this paper, three new Ruthenium(II) polypyridyl complexes containing ascididemin (ASC) as main ligand have been synthesized and characterized. Their interactions with different G-quadruplex (Htelo, c-myc and c-kit) (Htelo: human telomeric DNA, c-myc: cellular-myelocytomatosis viral oncogene, c-kit: oncogene c-kit promoter sequences) and duplex (ds26) DNA sequences were comparatively studied with the free ligand ASC by a series of spectroscopic techniques including UV-vis (ultraviolet-visible) spectroscopy, FID (fluorescent intercalator displacement) assay, and FRET (fluorescence resonance energy transfer) melting assay. Molecular docking studies were also performed to support the binding mode of the compounds with G-quadruplex DNA. Results indicated that [Ru(bpy)(2)ASC]center dot(PF6)(2) (1), [Ru(phen)(2)ASC]center dot(PF6)(2) (2), [Ru(tatp)(2)ASC]center dot(PF6)(2) (3) (bpy 2,2'-bipyridine, = phen = 1,10-phenanthroline, tatp = 1,4,8,9-tetra-aza-triphenylene) and ASC can effectively bind G-quadruplex and duplex DNA and stabilization ability lies in the order 3 > 2 > 1 > ASC. Complex 3 was determined to be the most promising candidate for further in vitro studies and potential anticancer drug.