硫氧还蛋白还原酶
硫氧还蛋白
硫醇
化学
谷胱甘肽
组合化学
还原酶
二硫键
二硫戊烷
基质(水族馆)
生物化学
酶
作者
Jan Felber,Lena Poczka,Karoline Scholzen,Lukas Zeisel,Martin S. Maier,Sander Busker,Ulrike Theisen,Christina Brandstädter,Katja Becker,Elias Arnér,Julia Ahlfeld,Oliver Thorn-Seshold
标识
DOI:10.26434/chemrxiv-2022-12k2f-v2
摘要
The cyclic five-membered disulfide 1,2-dithiolane has been used as the key element in numerous chemical biology probes. Contradictory views of this disulfide populate the literature: some reports describe it as being nonspecifically reduced, others as a highly specific substrate for thioredoxin reductase (TrxR). We here show that 1,2-dithiolane probes are nonspecifically reduced by a broad range of thiol reductants and redox-active proteins, and that their cellular performance is barely affected by TrxR inhibition or knockout. We conclude that inhibitor screenings and "TRFS" probes that have used 1,2-dithiolanes as TrxRselective substrates should be treated with caution, and may need re-evaluation. Understanding 1,2-dithiolanes’ behaviour needs consideration of probe localisation and environmentdependent fluorescence, reduction-independent ring-opening polymerisation, thiol-dependent cellular uptake, and caution when applying thiophilic inhibitors. We present an approach controlling against assay misinterpretation with reducible probes, to ensure that future TrxR-targeted designs are robustly evaluated for selectivity, and to better orient future research.
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