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首页> 外文期刊>Chemistry: A European journal >Dinuclear Ruthenium(II) Complexes That Induce and Stabilise G-Quadruplex DNA
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Dinuclear Ruthenium(II) Complexes That Induce and Stabilise G-Quadruplex DNA

机译：诱导和稳定G-四链体DNA的双核钌（II）配合物

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摘要

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 pi-pi 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.
机译：合成了一系列的双核钌（II）配合物，并确定该配合物是与端粒G-四链体DNA结合的新型高选择性化合物。通过使用圆二色性（CD）光谱，荧光共振能量转移（FRET）熔融测定，等温滴定量热法（ITC）和分子建模研究了这些复合物与端粒G-四链体DNA的相互作用。结果表明，复合物1、2和4在无盐或含有100 mm K +的缓冲液中诱导并稳定了端粒DNA反平行G四联体的形成。此外，复合物1和2牢固地结合并有效地稳定了端粒G-四链体结构，并且对G-四链体的选择性高于双链体DNA。相比之下，配合物3对G-四链体的影响要小得多，这表明拥有适当大小的平面以与G-四链体良好pi-pi堆叠对于双核钌（II）配合物与G-四链体的相互作用至关重要。 G四联体。此外，研究了四种复合物对端粒酶的抑制作用及其对细胞的作用，并确定复合物1是端粒酶和HeLa细胞增殖的最有希望的抑制剂。

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