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Interactions of ruthenium complexes containing indoloquinoline moiety with human telomeric G-quadruplex DNA.

Authors: Hui-juan HJ. Yu, Lin L. Yu, Zhi-feng ZF. Hao, Ying Y. Zhao
Published: 01/07/2014, Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy

Abstract

G-quadruplex structures are attractive targets for the development of anticancer drugs, as their formation in human telomere could impair telomerase activity, thus inducing apoptosis in cancer cells. Vast majority of G-quadruplex binding molecules have been designed and synthesized. Ruthenium complexes have also been reported to induction or stabilization of G-quadruplex structure of human telomeric sequence, whereas most of them generally promote the formation of antiparallel or hybrid-type G-quadruplex structure. Ruthenium complex that selectively promotes the formation of parallel G-quadruplex structure has rarely been reported. We reported here the interaction of two ruthenium complexes [Ru(bpy)2(mitatp)](2+)1 and [Ru(phen)2(mitatp)](2+)2 (bpy=2,2' bipyridine, phen=1,10-phenanthroline, mitatp=5-methoxy-isatino[1,2-b]-1,4,8,9-tetraazatriphenylene) containing indoloquinoline moiety with human telomeric G-quadruplex DNA (Telo22). Complex 1 binds to Telo22 tightly via a stable π-π stacking interaction and efficiently stabilizes the G-quadruplex structure. Circular dichroism (CD) spectra titration results suggest that complex 1 could induce Telo22 to fold into antiparallel G-quadruplex conformation. Complex 2 exhibits moderate G-quadruplex binding and stabilizing ability, while CD titration data reveals that complex 2 could promote the formation of parallel G-quadruplex structure.

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