A Nitroxide‐Tagged Platinum(II) Complex Enables the Identification of a DNA G‐Quadruplex Binding Mode |
| |
| Authors: | Dr. Cui‐Xia Xu Dr. Xiaojun Zhang Yi‐Wei Zhou Hanqiang Wang Dr. Qian Cao Dr. Yong Shen Prof. Dr. Liang‐Nian Ji Prof. Dr. Zong‐Wan Mao Prof. Dr. Peter Z. Qin |
| |
| Affiliation: | 1. MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry and Chemical Engineering, Sun Yat-Sen University, Guangzhou, Guangdong, P.R. China;2. Department of Chemistry, University of Southern California, Los Angeles, California, USA;3. Department of Chemistry, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong, P.R. China |
| |
| 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. |
| |
| Keywords: | EPR spectroscopy G-quadruplexes molecular docking nitroxide platinum(II) complexes |
|
|
