Regulation of multi-factors (tail/loop/link/ions) for G-quadruplex enantioselectivity of Δ- and Λ- [Ru(bpy)2(dppz-idzo)]2+

Abstract

Chiral recognition of DNA molecules is important because much evidence has indicated that transformations of chirality and diverse conformations of DNA are involved in a series of key biological events. Among these, enrichment of G-quadruplexes (GQs) in the genome, and the exploration of their multiple structures, has aroused great interest. Herein, we compared nearly 100 different sequences with 3′-tail sequences of variable length or different linkers or diverse loops and mutative ionic concentrations. All sequences were capable of forming stable GQs, with fluorescence signal enhancement upon binding with Δ- and Λ- [Ru(bpy)₂(dppz-idzo)]²⁺ (Δ/Λ-1). Our results show that multiple factors, including the 3′-tail length, linkers, loop length and ionic concentration, regulate the enantioselectivity of GQs. Furthermore, molecular docking simulations revealed that chiral recognition of GQs depends on the binding site. To the best of our knowledge, this is the first systematic study regarding the regulation of multi-factors for GQ selectivity of chiral Ru-complexes. These results will serve as a useful reference for enantioselective recognition of genomic GQs and may facilitate the development of chiral anticancer agents for targeting GQs.