Discovery of a Structural-Element Specific G-Quadruplex “Light-Up” Probe

The development of a fluorescent probe capable of detecting and distinguishing the wide diversity of G-quadruplex structures is particularly challenging. Herein, we report a novel BODIPY-based fluorescent sensor (GQR) that shows unprecedented selectivity to parallel-stranded G-quadruplexes with exposed ends and four medium grooves. Mechanistic studies suggest that GQR associates with G-quadruplex grooves close to the end of the tetrad core, which may explain the dye's specificity to only a subset of parallel structures. This specific recognition favours the disaggregation of GQR in aqueous solutions thereby recovering the inherent fluorescence of the dye. Due to its unique features, GQR represents a valuable tool for basic biological research and the rapid discovery of novel, specific ligands that target similar structural features of G-quadruplexes.