Binding of malachite green promotes stability and shows preference for a human telomere DNA G-quadruplex

Abstract

A single-stranded human telomere DNA sequence can fold into an intramolecular G-quadruplex structure, which has been shown to inhibit telomerase activity. Small molecules that selectively target and stabilise the G-quadruplex structure have been proposed as potential anticancer drugs. In this study, we analysed the properties of binding of malachite green, a cationic triphenylmethane dye, to the G-quadruplex of d[(T2AG3)4] by UV spectroscopy of thermal melting analysis, a competitive equilibrium dialysis assay, and absorption and circular dichroism spectroscopies. When binding to malachite green, the quadruplex structure that formed in the presence of K+ ions was stabilised with an increase in melting temperatures by 6 °C. Malachite green showed selective binding to the G-quadruplex in the presence of duplex and single-stranded DNAs, owing to which it presents higher potential for anticancer therapy, compared to other triphenylmethane dyes. The induced signals of circular dichroism indicate that the binding mode of malachite green involves intercalation between adjacent guanine tetrads of the G-quadruplex.