Abstract
Small molecule probes are indispensable tools to explore diverse cellular events. However, finding a specific probe of a target remains a high challenge. Here we report the discovery of Fast-TRFS, a specific and superfast fluorogenic probe of mammalian thioredoxin reductase, a ubiquitous enzyme involved in regulation of diverse cellular redox signaling pathways. By systematically examining the processes of fluorophore release and reduction of cyclic disulfides/diselenides by the enzyme, structural factors that determine the response rate and specificity of the probe are disclosed. Mechanistic studies reveal that the fluorescence signal is switched on by a simple reduction of the disulfide bond within the probe, which is in stark contrast to the sensing mechanism of published probes. The favorable properties of Fast-TRFS enable development of a high-throughput screening assay to discover inhibitors of thioredoxin reductase by using crude tissue extracts as a source of the enzyme.
Thioredoxin reductase (TrxR) plays a crucial part in regulating cellular redox
homeostasis. Here, the authors developed a fluorescent probe composed
of a five-membered disulphide, a coumarin fluorophore and a urea linker …
A fast and specific fluorescent probe for thioredoxin reductase that works via disulphide bond cleavage
期刊名：Nation Communications
文献编号：
文献地址： https://www.nature.com/articles/s41467-019-10807-8
发表日期： 21 June 2019
文献编号：
文献地址： https://www.nature.com/articles/s41467-019-10807-8
发表日期： 21 June 2019
