A far-red fluorescent probe for selective G-quadruplex DNA targeting

• Published in: Tetrahedron letters 2018-08, Vol.59 (34), p.3272-3278
• Main Authors: Zhang, Feng, Li, Gan, Lv, Fang-Lei, Jiang, Guang-Bin, Wang, Han-Xiang, Wang, Ming-Qi, Li, Shuo
• Format: Article
• Language: English
• Subjects: Far-red; Fluorescent probe; G-quadruplex; Styrylquinolinium scaffold
• ISSN: 0040-4039; 1873-3581
• DOI: 10.1016/j.tetlet.2018.07.037

[Display omitted] •A far-red fluorescent probe for G-quadruplex DNA targeting was developed.•The probe displayed excellent selectivity and sensitivity.•The detailed interactions of this probe with G-quadruplex DNAs were illustrated. The development of rapid and simple approaches for detection of G-quadruplex DNA structures has attracted significant attention to disclose their diverse physiological and pathological functions. Thiazole orange (TO) is a common fluorescence probe used for the detection of G-quadruplexes. However, it still suffers from some common problems like non-selective for G-quadruplex and emission in the lower wavelength region of spectrum, thus hampering its further applications. Probes with turn-on fluorescence in the far-red region are highly sought-after due to minimal auto-fluorescence and cellular damage. In this paper, we described a far-red fluorescent probe (L-1) by introducing an amine group into styrylquinolinium scaffold. The experimental results indicated that L-1 exhibited significant fluorescence enhancement when treated with G-quadruplexes but retained weak fluorescence in the presence of duplex DNAs. In addition, this probe also displayed higher binding affinity for parallel G-quadruplexes. The characteristics of L-1 were further investigated with UV–vis spectrophotometry, fluorescence, circular dichroism, KI quenching, FID assay and molecular docking to validate optical photophysical properties, as well as the selectivity, sensitivity and detailed binding mode toward G-quadruplex DNAs.