Department of Chemistry and Biochemistry, Swarthmore College, 500 College Ave., Swarthmore, PA, USA.
Department of Chemistry, Bryn Mawr College, Bryn Mawr, PA 19010, USA.
J Inorg Biochem. 2023 Dec;249:112388. doi: 10.1016/j.jinorgbio.2023.112388. Epub 2023 Sep 26.
Eight [Ru(bpy)L] and three [Ru(phen)L]complexes (where bpy = 2,2'-bipyridine and phen = 1,10-phenanthroline are ancillary ligands, and L = a polypyridyl experimental ligand) were investigated for their G-quadruplex binding abilities. Fluorescence resonance energy transfer melting assays were used to screen these complexes for their ability to selectively stabilize human telomeric DNA variant, Tel22. The best G-quadruplex stabilizers were further characterized for their binding properties (binding constant and stoichiometry) using UV-vis, fluorescence spectroscopy, and mass spectrometry. The ligands' ability to alter the structure of Tel22 was determined via circular dichroism and PAGE studies. We identified meallox as the experimental ligand capable of conferring excellent stabilizing ability and good selectivity to polypyridyl Ru(II) complexes. Replacing bpy by phen did not significantly impact interactions with Tel22, suggesting that binding involves mostly the experimental ligand. However, using a particular ancillary ligand can help fine-tune G-quadruplex-binding properties of Ru(II) complexes. Finally, the fluorescence "light switch" behavior of all Ru(II) complexes in the presence of Tel22 G-quadruplex was explored. All Ru(II) complexes displayed "light switch" properties, especially [Ru(bpy)(diamino)], [Ru(bpy)(dppz)], and [Ru(bpy)(aap)]. Current work sheds light on how Ru(II) polypyridyl complexes interact with human telomeric DNA with possible application in cancer therapy or G-quadruplex sensing.
研究了八个 [Ru(bpy)L] 和三个 [Ru(phen)L] 配合物（其中 bpy = 2,2'-联吡啶，phen = 1,10-菲咯啉是辅助配体，L = 多吡啶实验配体），以研究它们与 G-四链体的结合能力。荧光共振能量转移熔解实验用于筛选这些配合物选择性稳定人端粒 DNA 变体 Tel22 的能力。进一步使用紫外-可见分光光度法、荧光光谱法和质谱法对最佳 G-四链体稳定剂的结合特性（结合常数和化学计量）进行了表征。通过圆二色性和 PAGE 研究确定了配体改变 Tel22 结构的能力。我们确定 meallox 是一种实验配体，能够赋予多吡啶钌（II）配合物优异的稳定性和良好的选择性。用 phen 取代 bpy 不会显著影响与 Tel22 的相互作用，表明结合主要涉及实验配体。然而，使用特定的辅助配体可以帮助微调 Ru(II) 配合物与 G-四链体的结合特性。最后，研究了所有 Ru(II) 配合物在 Tel22 G-四链体存在下的荧光“光开关”行为。所有 Ru(II) 配合物都表现出“光开关”特性，尤其是 [Ru(bpy)(diamino)]、[Ru(bpy)(dppz)] 和 [Ru(bpy)(aap)]。目前的工作阐明了 Ru(II) 多吡啶配合物与人端粒 DNA 相互作用的方式，可能在癌症治疗或 G-四链体传感中有应用。
