title: Dinuclear ruthenium(II) complexes that induce and stabilise G-quadruplex DNA.
abstract: A series of dinuclear ruthenium(II) complexes were synthesised, and the complexes were determined to be new highly selective compounds for binding to telomeric G-quadruplex DNA. The interactions of these complexes with telomeric G-quadruplex DNA were studied by using circular dichroism (CD) spectroscopy, fluorescence resonance energy transfer (FRET) melting assays, isothermal titration calorimetry (ITC) and molecular modelling. The results showed that the complexes 1, 2 and 4 induced and stabilised the formation of antiparallel G-quadruplexes of telomeric DNA in the absence of salt or in the presence of 100 mM K(+)-containing buffer. Furthermore, complexes 1 and 2 strongly bind to and effectively stabilise the telomeric G-quadruplex structure and have significant selectivity for G-quadruplex over duplex DNA. In comparison, complex 3 had a much lesser effect on the G-quadruplex, suggesting that possession of a suitably sized plane for good π-π stacking with the G-quadruplets is essential for the interaction of the dinuclear ruthenium(II) complexes with the G-quadruplex. Moreover, telomerase inhibition by the four complexes and their cellular effects were studied, and complex 1 was determined to be the most promising inhibitor of both telomerase and HeLa cell proliferation.
authors.affiliation: MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry and Chemical Engineering, Sun Yat-Sen University, Guangzhou 510275 (P.R. China); School of Chemistry and Chemical Engineering, Guangdong Pharmaceutical University, Zhongshan, 528458 (China).
authors.forename: Li
authors.initials: L
authors.lastname: Xu
authors.forename: Xiang
authors.initials: X
authors.lastname: Chen
authors.forename: Jingheng
authors.initials: J
authors.lastname: Wu
authors.forename: Jinquan
authors.initials: J
authors.lastname: Wang
authors.forename: Liangnian
authors.initials: L
authors.lastname: Ji
authors.forename: Hui
authors.initials: H
authors.lastname: Chao
mesh_terms: D049109:Cell Proliferation / Q000187:drug effects*; D002942:Circular Dichroism; D056831:Coordination Complexes / Q000737:chemistry* / Q000494:pharmacology*; D004247:DNA / Q000737:chemistry*; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000378:metabolism; D031541:Fluorescence Resonance Energy Transfer; D054856:G-Quadruplexes; D006367:HeLa Cells / Q000737:chemistry*; D006801:Humans; D008968:Molecular Conformation; D012428:Ruthenium / Q000737:chemistry; D019098:Telomerase / Q000037:antagonists & inhibitors* / Q000737:chemistry* / Q000378:metabolism
chemical_list: D056831:Coordination Complexes; D004791:Enzyme Inhibitors; D012428:Ruthenium; D004247:DNA; D019098:Telomerase
keywords: DNA; G-quadruplexes; conformation analysis; ruthenium; telomeres