钌-吲哚喹喔啉配合物与G-四链体的作用研究.docVIP

  Ru-Indoloquinoline Complex as a Selective and Effective Human Telomeric G-quadruplex Binder# Yu Huijuan* 5 10 15 20 (School of Chemical Engineering and Light Industry, Guangdong University of Technolog,) Abstract: Indoloquinoline and its derivatives have been reported to be a kind of efficient G-quadruplex binderand have been found to interact preferentially to intramolecular G-qudruplex and inhibit telomerase activity in human K562 cells and SW620 cells. In contrast to indoloquinoline derivatives, much less is known about the metal complex based on indoloquinoline or its derivative. In this report, we studied the interaction of ruthenium complex [Ru(bpy)2(itatp)]2+ which containg indoloquinoline moiety with human telomeric G-quadruplex DNA (Telo22) and c-myc G-quadruplex DNA (Pu27) by UV-visible (UV-Vis), fluorescence spectroscopy, fluorescent intercalator displacement (FID), thermal denaturation studies and CD spectroscopy. The results suggest that [Ru(bpy)2(itatp)]2+ displays a strong π-π stacking interaction with human telomeric G-quadruplex with a high binding constant (~107 M-1), but just exhibits slight binding affinity to c-myc G-quadruplex, thus showing significant selectivity over human telomeric G-quadruplex. The CD titration results indicate that [Ru(bpy)2(itatp)]2+ could effectively convert Telo22 into antiparallel G-quadruplex conformation, while in the c-myc G-quadruplex case, instead of promoting Pu27 to fold into G-quadruplex, [Ru(bpy)2(itatp)]2+ destroys the parallel G-quadruplex structure of Pu27. Key words: G-quadruplex; Telomere; Ruthenium complex; Indoloquinoline  0  Introduction DNA is the principal genetic molecule in biological systems, and is known to adopt right handed duplex structure B-DNA. However, the structure of DNA is polymorphic, a number of alternative structures non-B DNA, such as Z-DNA, hairpins, cruciform, and quadruplex, have 25 30 35 40 45 been identified and found to be unstable and mutagenic [1-3]. Among these n