Ribaudo Giovanni, Oselladore Erika, Ongaro Alberto, Zagotto Giuseppe, Memo Maurizio, Gianoncelli Alessandra
Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy.
Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Padova, Italy.
Nat Prod Res. 2022 Jul;36(13):3469-3473. doi: 10.1080/14786419.2020.1859505. Epub 2020 Dec 12.
In drug discovery, ligand-mediated stabilization of G-quadruplexes is pursued for regulating gene expression and key cellular processes. Electrospray ionization mass spectrometry (ESI-MS) has been optimized for screening putative DNA-binding small molecules of natural and synthetic origin. Several flavonoids were reported to interact with G-quadruplex, and quercetin is among them. In this contribution, the interaction with G-quadruplex DNA of rutin, a glycoside of quercetin extracted from flower buds of (L.) Schott, was investigated by means of ESI-MS and molecular docking. While rutin and quercetin showed similar G-quadruplex binding affinity values, rutin was characterized by enhanced selectivity for G-quadruplex over double stranded DNA. Moreover, collision-induced dissociation (CID) assays demonstrated that rutin stabilizes the G-quadruplex arrangement more efficiently, and molecular docking predicted stacking as the preferential interaction pattern.
在药物研发中，人们致力于通过配体介导的方式稳定G-四链体，以调控基因表达和关键细胞过程。电喷雾电离质谱（ESI-MS）已得到优化，用于筛选天然和合成来源的假定DNA结合小分子。据报道，几种黄酮类化合物可与G-四链体相互作用，槲皮素就是其中之一。在本研究中，通过ESI-MS和分子对接的方法，研究了从槐（L.）肖特花芽中提取的槲皮素糖苷芦丁与G-四链体DNA的相互作用。虽然芦丁和槲皮素显示出相似的G-四链体结合亲和力值，但芦丁对G-四链体的选择性高于双链DNA。此外，碰撞诱导解离（CID）分析表明，芦丁能更有效地稳定G-四链体结构，分子对接预测堆积是其优先的相互作用模式。
