Targeting G-quadruplex Structures with Extrinsic Probes: Prospect of Selective and Efficient G- quadruplex Inducers in Therapeutics

The research on the G-quadruplex DNAs has received much attention in recent years and numerous reports appeared probing its detection, structure, stability, reactivity and selectivity, aimed mainly for the chemical intervention of specific biological activity or sensor applications. Our study has demonstrated the use of a fluorogenic dye, Thioflavin T, to stabilize the telomeric DNA strand into a G-quadruplex structure under physiological conditions. We have assessed several other DNA forms and set appropriate conditions to achieve highly selective interaction of the probe with the G-quadruplex structure. In addition, the dye becomes highly fluorescent, more than 2000 times brighter, increasing the sensitivity for the optical detection of the G-quadruplex in the cellular environment against other DNA forms. This work reveals the applicability of Thioflavin T to inhibit telomerase activity and opens up avenues to explore new dyes/drugs based on ThT scaffold, which have the potential to highly specific quadruplex inducing/sensing agents for cancer therapeutics.