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  • Title: Targeting telomeric G-quadruplexes with the ruthenium(II) complexes [Ru(bpy)(2)(ptpn)](2+) and [Ru(phen)(2)(ptpn)](2+).
    Author: Chen X, Wu JH, Lai YW, Zhao R, Chao H, Ji LN.
    Journal: Dalton Trans; 2013 Apr 07; 42(13):4386-97. PubMed ID: 23400220.
    Abstract:
    Two ruthenium(II) polypyridyl complexes, [Ru(bpy)(2)(ptpn)](2+) (1) (bpy = 2,2'-bipyridine, ptpn = 3-(1,10-phenanthroline-2-yl)-as-triazino[5,6-f]1,10-phenanthroline) and [Ru(phen)(2)(ptpn)](2+) (2) (phen = 1,10-phenanthroline), were synthesized and characterized. Crystal structure analysis shows that complex 1 has a large planar aromatic area and possesses the potential to fit the geometric structure of G-quadruplex. The interaction of the G-quadruplex DNA with Ru(ii) complexes was explored by means of circular dichroism (CD), fluorescence resonance energy transfer (FRET) melting assay, competitive FRET assay and polymerase chain reaction (PCR) stop assay. The results indicated that complexes 1 and 2 both have the ability to promote the formation and stabilization of the human telomeric d[(TTAGGG)(n)] (HTG22) quadruplex and exhibit high G-quadruplex DNA selectivity over duplex DNA. The telomere repeat amplification protocol (TRAP) assay and long-term proliferation experiments further demonstrate that the Ru(II) complexes are potent telomerase inhibitors and HeLa cell proliferation inhibitors.
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