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A Nitroxide‐Tagged Platinum(II) Complex Enables the Identification of a DNA G‐Quadruplex Binding Mode
Author(s) -
Xu CuiXia,
Zhang Xiaojun,
Zhou YiWei,
Wang Hanqiang,
Cao Qian,
Shen Yong,
Ji LiangNian,
Mao ZongWan,
Qin Peter Z.
Publication year - 2016
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201504960
Subject(s) - g quadruplex , nitroxide mediated radical polymerization , dna , platinum , identification (biology) , computational biology , chemistry , biophysics , biology , biochemistry , radical polymerization , organic chemistry , copolymer , catalysis , polymer , botany
We reported a novel strategy for investigating small molecule binding to G‐quadruplexes (GQs). A newly synthesized dinuclear platinum(II) complex (Pt 2 L) 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 Pt 2 L and hTel GQ. Measurements indicated that two molecules of Pt 2 L bind with one molecule of hTel GQ. The inter‐spin distance measured between the two bound Pt 2 L, together with molecular docking analyses, revealed that Pt 2 L 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.