State Key Laboratory of Elemento-Organic Chemistry and Department of Chemical Biology, College of Chemistry, National Pesticide Engineering Research Center, Collaborative Innovation Center of Chemical Science and Engineering, Nankai University, Tianjin, 300071, China.
State Key Laboratory of Organic-Inorganic Composites and Beijing Key Lab of Bioprocess, Beijing University of Chemical Technology (BUCT), Beijing 100029, China.
Org Biomol Chem. 2021 Jul 28;19(29):6527-6533. doi: 10.1039/d1ob01114f.
In order to evaluate 7-sulfonamide benzoxadiazole (SBD) derivatives for the development of fluorescent probes, herein we investigated the thiolysis reactivity and selectivity of a series of SBD compounds with different atoms (N/O/S/Se) at the 4-position. Both SBD-amine and SBD-ether are stable toward biothiols in buffer (pH 7.4), while SBD-selenoether can react efficiently with biothiols GSH/Hcy, Cys, and H2S to produce SBD-SG/S-Hcy, SBD-NH-Cys, and SBD-SH, respectively, with three different sets of spectral signals. Therefore, the SBD-selenoether compounds should be useful platforms for the differentiation of these biothiols. Though SBD-alkylthioether shows much lower reactivity than SBD-selenoether, SBD-arylthioether is a tunable motif and structural modifications at the aryl moiety enable the rate of thiol-mediated thiolysis to be modified. To this end, an ER-targeted GSH-selective fluorescent probe 7 was rationally designed via thiolysis of SBD-arylthioether. Compared with control probe SBD-Cl, probe 7 exhibits improved GSH selectivity and better biocompatibility. In total, this study highlights that the modification at the 4-position of SBD is an efficient strategy for the development of new fluorescent probes with tunable reactivity and selectivity.
为了评估 7-磺酰胺苯并二唑（SBD）衍生物在荧光探针开发方面的应用，本文研究了一系列 4 位不同原子（N/O/S/Se）取代的 SBD 化合物的硫解反应活性和选择性。SBD-胺和 SBD-醚在缓冲液（pH 7.4）中对生物硫醇稳定，而 SBD-硒醚可以与 GSH/Hcy、半胱氨酸和 H2S 等生物硫醇高效反应，分别生成 SBD-SG/S-Hcy、SBD-NH-Cys 和 SBD-SH，具有三组不同的光谱信号。因此，SBD-硒醚化合物应该是区分这些生物硫醇的有用平台。虽然 SBD-烷基硫醚的反应活性远低于 SBD-硒醚，但 SBD-芳基硫醚是一个可调的结构，芳基部分的结构修饰可以调节硫醇介导的硫解反应速率。为此，通过 SBD-芳基硫醚的硫解反应，合理设计了一种 ER 靶向的 GSH 选择性荧光探针 7。与对照探针 SBD-Cl 相比，探针 7 表现出更好的 GSH 选择性和更好的生物相容性。总之，本研究强调了 SBD 4 位的修饰是开发具有可调反应性和选择性的新型荧光探针的有效策略。
