Department of Chemistry, Portland State University, 1719 SW 10th Avenue, Portland, OR, 97201, USA.
Department of Dermatology, Oregon Health & Science University, Portland, OR, 97201, USA.
Angew Chem Int Ed Engl. 2020 Aug 24;59(35):15147-15151. doi: 10.1002/anie.202004094. Epub 2020 Jun 17.
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 ) of 15.89 μm. 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.
我们报道了首个基于二硒键的探针,用于选择性检测硫氧还蛋白还原酶(TrxR),这种酶在黑色素瘤中通常过表达。探针的设计涉及将半萘并荧光染料与二硒键部分连接。TrxR 还原二硒键,触发探针的荧光开启响应。动力学研究表明,探针与 TrxR 具有有利的结合,米氏常数(K )为 15.89 μm。计算对接模拟预测,与二硫键类似物相比,该探针与 TrxR 活性位点具有更大的结合亲和力。体外成像研究进一步证实,与二硫键类似物相比,二硒键探针显示出改善的 TrxR 活性信号。