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二镍-双酚配合物作为人端粒二聚体G-四链体的结合剂

Dinickel-Salphen Complexes as Binders of Human Telomeric Dimeric G-Quadruplexes.

作者信息

Zhou Chun-Qiong, Liao Ting-Cong, Li Zi-Qi, Gonzalez-Garcia Jorge, Reynolds Matthew, Zou Min, Vilar Ramon

机构信息

Department of Chemistry, Imperial College London, South Kensington, London, SW72AZ, UK.

Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, 510515, P. R. China.

出版信息

Chemistry. 2017 Apr 3;23(19):4713-4722. doi: 10.1002/chem.201700276. Epub 2017 Mar 24.

Abstract

Three new polyether-tethered dinickel-salphen complexes (2 a-c) have been synthesized and fully characterized by NMR spectroscopy, mass spectrometry, and elemental analyses. The binding affinity and selectivity of these complexes and of the parent mono-nickel complex (1) towards dimeric quadruplex DNA have been determined by UV/Vis titrations, fluorescence spectroscopy, CD spectroscopy, and electrophoresis. These studies have shown that the dinickel-salphen complex with the longest polyether linker (2 c) has higher binding affinity and selectivity towards dimeric quadruplexes (over monomeric quadruplexes) than the dinickel-salphen complexes with the shorter polyether linkers (2 a and 2 b). Complex 2 c also has higher selectivity towards human telomeric dimeric quadruplexes with one TTA linker than the monometallic complex 1. Based on the spectroscopic data, a possible binding mode between complex 2 c and the dimeric G-quadruplex DNA under study is proposed.

摘要

已合成了三种新的聚醚连接的二镍-双水杨醛缩邻苯二胺配合物(2 a - c),并通过核磁共振光谱、质谱和元素分析对其进行了全面表征。通过紫外/可见滴定、荧光光谱、圆二色光谱和电泳测定了这些配合物以及母体单镍配合物(1)对二聚体四链体DNA的结合亲和力和选择性。这些研究表明,具有最长聚醚连接基的二镍-双水杨醛缩邻苯二胺配合物(2 c)对二聚体四链体(相对于单体四链体)的结合亲和力和选择性高于具有较短聚醚连接基的二镍-双水杨醛缩邻苯二胺配合物(2 a和2 b)。配合物2 c对具有一个TTA连接基的人端粒二聚体四链体的选择性也高于单金属配合物1。基于光谱数据,提出了配合物2 c与所研究的二聚体G-四链体DNA之间可能的结合模式。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f19c/5516229/84e843c26be2/CHEM-23-4713-g001.jpg

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