Decrease of Protein Vicinal Dithiols in Parkinsonism Disclosed by a Monoarsenical Fluorescent Probe
journal contributionposted on 04.03.2020, 17:06 by Guodong Hu, Huiyi Jia, Yanan Hou, Xiao Han, Lu Gan, Jing Si, Dong-Hyung Cho, Hong Zhang, Jianguo Fang
Vicinal dithiol-containing proteins (VDPs) play an important role in maintaining the structures and functions of proteins mainly through the conversion between dithiols and disulfide bonds. The content of VDPs also reflects the redox status of an organism. To specifically and expediently detect VDPs, we developed a turn-on monoarsenical fluorescent probe (NEP) based on the intramolecular charge transfer mechanism. Naphthalimide was chosen as a fluorophore and linked with the receptor moiety (cyclic dithiarsolane) via carbamate segment. In the presence of VDPs, NEP displays a strong green fluorescence signal produced by the cyclic dithiarsolane cleavage and subsequent intramolecular cyclization to liberate the fluorophore. Furthermore, NEP exhibits high selectivity toward VDPs over other protein thiols and low molecular weight thiols. The favorable properties of NEP enable it readily to detect VDPs in live cells and in vivo. In addition, a remarkable decrease of VDPs in parkinsonism was disclosed for the first time, highlighting that regulating VDPs level has a therapeutic potential for parkinsonism.
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NEP exhibitsProbe Vicinal dithiol-containing proteinsprotein thiolsProtein Vicinal Dithiolsredox statusNEP displayscarbamate segmentcyclic dithiarsolane cleavagecyclic dithiarsolaneturn-on monoarsenicalfluorescence signalVDPs levelintramolecular cyclizationreceptor moietydisulfide bondsweight thiolsintramolecular charge transfer mechanism