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.

近年来，对用于诊断和治疗应用的G-四链体的兴趣日益增长。这就要求开发能够在大量G-四链体中区分特定结构的高选择性探针。然而，迄今为止，很少有探针对特定的G-四链体结构表现出令人满意的选择性。在这项研究中，我们通过在商业花青染料噻唑橙（TO）上引入一个额外的苯并噻唑部分，设计了一种名为TO-BTZ的新探针。通过特异性靶向5'端G四联体附近形成的独特结合位点，TO的这种修饰显着调整了其对杂合端粒G-四链体DNA的选择性。这种特定的相互作用分解了TO-BTZH聚集到其单体上，并进一步阻碍TO-BTZ单体的分子旋转，从而导致荧光增强。此外，我们观察到TO-BTZ具有检测细胞中端粒G-四链体的潜力。两者合计，这项工作将为寻找可以区分不同G-四链体结构的新一代探针提供启发。