title: A Nitroxide-Tagged Platinum(II) Complex Enables the Identification of DNA G-Quadruplex Binding Mode.
abstract: We reported a novel strategy for investigating small molecule binding to G-quadruplexes (GQs). A newly synthesized dinuclear platinum(II) complex (Pt2L) 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 Pt2L and hTel GQ. Measurements indicated that two molecules of Pt2L bind with one molecule of hTel GQ. The inter-spin distance measured between the two bound Pt2L, together with molecular docking analyses, revealed that Pt2L 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.
authors: MOE Key Laboratory of Bioinorganic and Synthetic Chemistry School of Chemistry and Chemical Engineering, Sun Yat-Sen University Guangzhou, Guangdong, 510275 (P.R. China).
authors: Cui-Xia
authors: CX
authors: Xu
authors: Department of Chemistry, University of Southern California Los Angeles, California, 90089 (USA).
authors: Xiaojun
authors: X
authors: Zhang
authors: MOE Key Laboratory of Bioinorganic and Synthetic Chemistry School of Chemistry and Chemical Engineering, Sun Yat-Sen University Guangzhou, Guangdong, 510275 (P.R. China).
authors: Yi-Wei
authors: YW
authors: Zhou
authors: MOE Key Laboratory of Bioinorganic and Synthetic Chemistry School of Chemistry and Chemical Engineering, Sun Yat-Sen University Guangzhou, Guangdong, 510275 (P.R. China).
authors: Hanqiang
authors: H
authors: Wang
authors: MOE Key Laboratory of Bioinorganic and Synthetic Chemistry School of Chemistry and Chemical Engineering, Sun Yat-Sen University Guangzhou, Guangdong, 510275 (P.R. China).
authors: Qian
authors: Q
authors: Cao
authors: MOE Key Laboratory of Bioinorganic and Synthetic Chemistry School of Chemistry and Chemical Engineering, Sun Yat-Sen University Guangzhou, Guangdong, 510275 (P.R. China).
authors: Yong
authors: Y
authors: Shen
authors: MOE Key Laboratory of Bioinorganic and Synthetic Chemistry School of Chemistry and Chemical Engineering, Sun Yat-Sen University Guangzhou, Guangdong, 510275 (P.R. China).
authors: Liang-Nian
authors: LN
authors: Ji
authors: MOE Key Laboratory of Bioinorganic and Synthetic Chemistry School of Chemistry and Chemical Engineering, Sun Yat-Sen University Guangzhou, Guangdong, 510275 (P.R. China).
authors: Zong-Wan
authors: ZW
authors: Mao
authors: Department of Chemistry, University of Southern California Los Angeles, California, 90089 (USA).
authors: Peter Z
authors: PZ
authors: Qin
mesh_terms: D001665:Binding Sites; D002942:Circular Dichroism; D056831:Coordination Complexes / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D004247:DNA / Q000737:chemistry / Q000378:metabolism; D004578:Electron Spin Resonance Spectroscopy; D054856:G-Quadruplexes / Q000187:drug effects*; D006801:Humans; D062105:Molecular Docking Simulation; D009589:Nitrogen Oxides / Q000737:chemistry*; D009690:Nucleic Acid Conformation; D010984:Platinum / Q000737:chemistry*; D019098:Telomerase / Q000037:antagonists & inhibitors / Q000378:metabolism; D016615:Telomere / Q000737:chemistry; D044366:Transition Temperature
chemical_list: D056831:Coordination Complexes; D009589:Nitrogen Oxides; D010984:Platinum; D004247:DNA; D019098:Telomerase; C039900:nitroxyl
keywords: EPR spectroscopy; G-quadruplexes; molecular docking; nitroxide; platinum(II) complexes