Department of Food, Environmental and Nutritional Sciences (DEFENS), University of Milan (Università degli Studi di Milano), 20133 Milan, Italy.
National Institute of Fundamental Studies, Kandy 20000, Sri Lanka.
Int J Mol Sci. 2022 Dec 16;23(24):16018. doi: 10.3390/ijms232416018.
G-quadruplexes are nucleotide sequences present in the promoter region of numerous oncogenes, having a key role in the suppression of gene transcription. Recently, the binding of anthraquinones from to G-quadruplex structures has been studied through various physico-chemical techniques. Intrigued by the reported results, we investigated the affinity of aloe emodin, aloe emodin-8-glucoside, and aloin to selected G-quadruplex nucleotide sequences by NMR spectroscopy. The structural determinants for the formation of the ligand/nucleotide complexes were elucidated and a model of the interactions between the tested compounds and and G-quadruplex DNA structures was built by integrated NMR and molecular modeling studies. Overall, the obtained results confirmed and implemented the previously reported findings, pointing out the complementarity of the different approaches and their contribution to a more detailed overview of the ligand/nucleotide complex formation. Furthermore, the proposed models of interaction could pave the way to the design of new nature-derived compounds endowed with increased G-quadruplex stabilizing activity.
G-四链体是存在于许多癌基因启动子区域的核苷酸序列，在基因转录抑制中具有关键作用。最近，通过各种物理化学技术研究了蒽醌类化合物与 G-四链体结构的结合。受报道结果的启发，我们通过 NMR 光谱研究了芦荟大黄素、芦荟大黄素-8-葡萄糖苷和芦荟苷与选定的 G-四链体核苷酸序列的亲和力。阐明了形成配体/核苷酸复合物的结构决定因素，并通过整合 NMR 和分子建模研究构建了测试化合物与 和 G-四链体 DNA 结构之间相互作用的模型。总的来说，获得的结果证实并实施了先前的报告结果，指出了不同方法的互补性及其对配体/核苷酸复合物形成的更详细概述的贡献。此外，所提出的相互作用模型可以为设计具有增强的 G-四链体稳定活性的新型天然衍生化合物铺平道路。
