Preferential Binding of a Red Emissive Julolidine Derivative to a Promoter G-Quadruplex.

Abstract

The therapeutic potential of G-quadruplexes has increased significantly with the growing understanding of their functional roles in pathogens apart from human diseases such as cancer. Here, we report the synthesis of three julolidine-based molecules and their binding to nucleic acids. Among the synthesized molecules, compound 1 exhibited red emissive fluorescence with a distinct preference for Pu22 G-quadruplex. The binding of compound 1 to Pu22 G-quadruplex, initially identified through a fluorescence-based screening, was further confirmed by UV-vis, fluorescence spectroscopy, and circular dichroism-based experiments. Thermal denaturation of compound 1 in the presence of Pu22 G-quadruplex revealed a concentration-dependent stabilization (~10.0 °C at 1 : 3 stoichiometry). Fluorescence-based experiments revealed 1 : 1 stoichiometry of the interaction and an association constant (Ka ) of 5.67×106  M-1 . CD experiments displayed that the parallel conformation of the G-quadruplex was retained on compound 1's binding and signs of higher order binding/complex formation were observed at high compound 1 to DNA ratio. Molecular docking studies revealed the dominance of stacking and van der Waals interactions in the molecular recognition which was aided by some close-distance interactions involving the quinolinium nitrogen atom.