Decrease of Protein Vicinal Dithiols in Parkinsonism Disclosed by a Monoarsenical Fluorescent Probe

Abstract

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.

Thiol-Mediated Uptake

“… 143 , 144 Exofacial neighboring thiols have been imaged with such fluorescent arsonodithioite exchangers. 23 − 25 Phenyl arsine oxides were also shown early on to inhibit the entry of HIV virus about as efficiently as DTNB. 8 In clear contrast, thiol-mediated uptake and its inhibition remain a fascinating topic to be explored with dynamic covalent pnictogen chemistry, including possible contributions of turned-on noncovalent pnictogen bonds into deepened σ holes.…”

Structural Modification of Aminophenylarsenoxides Generates Candidates for Leukemia Treatment via Thioredoxin Reductase Inhibition

“…Gathering lines of evidences suggested that trivalent arsenicals interacted readily with vicinal dithiol-containing proteins. ,,− TrxR has a C-terminal active site as the sequence of −Gly–Cys–Sec–Gly–COOH, and this spatially close thiol/selenol pair is exposed on the TrxR surface. Our previous study and the recent work by Zhang et at .…”

Fluorescent Probes for Imaging Protein Disulfides in Live Organisms

“…We also treated the cells with varying concentrations of H 2 O 2 , and a dose-dependent increase of the fluorescence signal was observed (Figure B). Zebrafishes have been widely used as a model vertebrate in biomedical research. − We further demonstrated that the probe is readily applied to image PDS in zebrafishes (Figure C).…”