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A Diselenide Turn‐On Fluorescent Probe for the Detection of Thioredoxin Reductase
Author(s) -
Mafireyi Tendai J.,
Laws Madeleine,
Bassett John W.,
Cassidy Pamela B.,
Escobedo Jorge O.,
Strongin Robert M.
Publication year - 2020
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.202004094
Subject(s) - thioredoxin reductase , diselenide , moiety , fluorescence , chemistry , diphenyl diselenide , thioredoxin , enzyme , biophysics , biochemistry , stereochemistry , selenium , biology , organic chemistry , physics , quantum mechanics
We report the first diselenide‐based probe for the selective detection of thioredoxin reductase (TrxR), an enzyme commonly overexpressed in melanomas. The probe design involves conjugation of a seminaphthorhodafluor dye with a diselenide moiety. TrxR reduces the diselenide bond, triggering a fluorescence turn‐on response of the probe. Kinetic studies reveal favorable binding of the probe with TrxR with a Michaelis–Menten constant ( K m ) of 15.89 μ m . Computational docking simulations predict a greater binding affinity to the TrxR active site in comparison to its disulfide analogue. In vitro imaging studies further confirmed the diselenide probe exhibited improved signaling of TrxR activity compared to the disulfide analogue.