Enhanced G-quadruplex selectivity of flavonoid glycoside rutin over quercetin

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 Styphnolobium japonicum (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.