Institute of Fluorescent Probes for Biological Imaging, School of Chemistry and Chemical Engineering, School of Materials Science and Engineering , University of Jinan , Jinan , Shandong 250022 , P.R. China.
Anal Chem. 2019 Feb 19;91(4):2932-2938. doi: 10.1021/acs.analchem.8b05116. Epub 2019 Feb 1.
A complicated relationship between the active small molecules exists in cells. On the organelle level, active small molecules also play an important role in the maintenance of organelle functions and roles. To investigate the relationship of biomolecules in subcellular, it is necessary and critical to develop molecular tools that can track two kinds of associated biomolecules within organelles with multiple fluorescence signals. However, this is still an unmet challenge up to date. Herein, we present the first single-fluorescent probe (Lyso-HA-HS) that can detect oxidative (HOCl) and reductive (HS) substances within an organelle (lysosomes) with multiresponse signals. The reactions of the new probe with HS and HOCl simultaneously result in the blue and red channels emissions, respectively, providing different signal responses to the oxidative and reductive substances in the cellular lysosomes. Using a single fluorescent probe, we first achieved dual-channel imaging of the endogenous hypochlorous acid and hydrogen sulfide, respectively, in the lysosomes in the living cells. Moreover, the highly desirable attributes of the probe Lyso-HA-HS (such as high selectivity, good membrane-permeability, and lysosome enrichment ability) may enable it to be used in revealing the relationship of HOCl and HS in lysosomes.
细胞内的活性小分子之间存在着复杂的关系。在细胞器水平上,活性小分子在维持细胞器功能和角色方面也起着重要作用。为了研究亚细胞内生物分子的关系,开发能够在细胞器内用多种荧光信号追踪两种相关生物分子的分子工具是必要的和关键的。然而,这至今仍是一个尚未满足的挑战。在此,我们提出了第一个能够在细胞器(溶酶体)内用多响应信号检测氧化(HOCl)和还原(HS)物质的单荧光探针(Lyso-HA-HS)。新探针与 HS 和 HOCl 的反应分别导致蓝、红通道的发射,分别为细胞溶酶体中氧化和还原物质提供不同的信号响应。我们使用单个荧光探针,首次在活细胞的溶酶体中分别实现了内源性次氯酸和硫化氢的双通道成像。此外,探针 Lyso-HA-HS 的高度理想的特性(如高选择性、良好的膜通透性和溶酶体富集能力)可能使其能够用于揭示溶酶体中 HOCl 和 HS 的关系。