Biophysical probing of the binding properties of a Cu(II) complex with G-quadruplex DNA: an experimental and computational study.

Telomerase inhibition through G-quadruplex stabilization by small molecules is of great interest as a novel anticancer therapeutic strategy. Here, we show that newly synthesized Cu-complex binds to G-quadruplex DNA and induces changes in its stability. This biophysical interaction was investigated in vitro using spectroscopic, voltammetric and computational techniques. The binding constant for this complex to G-quadruplex using spectroscopic and electrochemical methods is in the order of 10(5) . The binding stoichiometry was investigated using spectroscopic techniques and corresponded to a ratio of 1: 1. Fluorescence titration results reveal that Cu-complex is quenched in the presence of G-quadruplex DNA. Analysis of the fluorescence emission at different temperatures shows that ΔH° > 0, ΔS° > 0 and ΔG° < 0, and indicates that hydrophobic interactions played a major role in the binding processes. MD simulation results suggested that this ligand could stabilize the G-quadruplex structure. An optimized docked model of the G-quadruplex-ligand mixture confirmed the experimental results. Based on the results, we conclude that Cu-complex as an anticancer candidate can bind and stabilize the G-quadruplex DNA structure.