Tuning the selectivity of a commercial cyanine nucleic acid dye for preferential sensing of hybrid telomeric G-quadruplex DNA

Abstract

Recent years have witnessed an ever-increasing interest in G-quadruplexes for diagnostic and therapeutic applications. This calls for the development of highly selective probes that can differentiate a particular structure among large quantities of G-quadruplexes. However, to this day, there are few probes that show satisfactory selectivity for a particular G-quadruplex structure. In this study, we engineered a new probe called TO-BTZ by introducing an additional benzothiazole moiety on a commercial cyanine dye thiazole orange (TO). Such a modification of TO significantly tuned its selectivity toward the hybrid telomeric G-quadruplex DNA by specifically targeting the unique binding site formed near the 5′-end G-quartet. Such specific interactions disassembled the TO-BTZ H-aggregate to its monomers and further hindered the molecular rotation of the TO-BTZ monomer, thus leading to fluorescence enhancement. Furthermore, we observed that TO-BTZ has the potential to sense telomeric G-quadruplexes in cells. Taken together, this work will shed light on the search for a new generation of probes that can distinguish between different G-quadruplex structures.