Xu Cui-Xia, Zhang Xiaojun, Zhou Yi-Wei, Wang Hanqiang, Cao Qian, Shen Yong, Ji Liang-Nian, Mao Zong-Wan, Qin Peter Z
MOE Key Laboratory of Bioinorganic and Synthetic Chemistry School of Chemistry and Chemical Engineering, Sun Yat-Sen University Guangzhou, Guangdong, 510275 (P.R. China).
Department of Chemistry, University of Southern California Los Angeles, California, 90089 (USA).
Chemistry. 2016 Mar 1;22(10):3405-3413. doi: 10.1002/chem.201504960. Epub 2016 Feb 4.
We reported a novel strategy for investigating small molecule binding to G-quadruplexes (GQs). A newly synthesized dinuclear platinum(II) complex (PtL) containing a nitroxide radical was shown to selectively bind a GQ-forming sequence derived from human telomere (hTel). Using the nitroxide moiety as a spin label, electron paramagnetic resonance (EPR) spectroscopy was carried out to investigate binding between PtL and hTel GQ. Measurements indicated that two molecules of PtL bind with one molecule of hTel GQ. The inter-spin distance measured between the two bound PtL, together with molecular docking analyses, revealed that PtL predominately binds to the neighboring narrow and wide grooves of the G-tetrads as hTel adopts the antiparallel conformation. The design and synthesis of nitroxide tagged GQ binders, and the use of spin-labeling/EPR to investigate their interactions with GQs, will aid the development of small molecules for manipulating GQs involved in crucial biological processes.
我们报道了一种研究小分子与G-四链体（GQs）结合的新策略。一种新合成的含氮氧化物自由基的双核铂（II）配合物（PtL）被证明能选择性地结合源自人类端粒（hTel）的GQ形成序列。以氮氧化物部分作为自旋标记，利用电子顺磁共振（EPR）光谱研究PtL与hTel GQ之间的结合。测量结果表明，两个PtL分子与一个hTel GQ分子结合。两个结合的PtL之间测得的自旋间距离以及分子对接分析表明，由于hTel采取反平行构象，PtL主要结合到G-四联体相邻的窄沟和宽沟处。氮氧化物标记的GQ结合剂的设计与合成，以及利用自旋标记/EPR研究它们与GQs的相互作用，将有助于开发用于调控参与关键生物过程的GQs的小分子。
