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| Fältnamn | Indikatorer | Metadata |
|---|---|---|
| 000 | 02622naa a2200385 4500 | |
| 001 | oai:prod.swepub.kib.ki.se:149246184 | |
| 003 | SwePub | |
| 008 | 240701s2022 | |||||||||||000 ||eng| | |
| 024 | 7 | a http://kipublications.ki.se/Default.aspx?queryparsed=id:1492461842 URI |
| 024 | 7 | a https://doi.org/10.1038/s41467-022-29136-42 DOI |
| 040 | a (SwePub)ki | |
| 041 | a engb eng | |
| 042 | 9 SwePub | |
| 072 | 7 | a ref2 swepub-contenttype |
| 072 | 7 | a art2 swepub-publicationtype |
| 100 | 1 | a Felber, JG4 aut |
| 245 | 1 0 | a Cyclic 5-membered disulfides are not selective substrates of thioredoxin reductase, but are opened nonspecifically |
| 264 | c 2022-04-01 | |
| 264 | 1 | b Springer Science and Business Media LLC,c 2022 |
| 520 | a The cyclic five-membered disulfide 1,2-dithiolane has been widely used in chemical biology and in redox probes. Contradictory reports have described it either as nonspecifically reduced in cells, or else as a highly specific substrate for thioredoxin reductase (TrxR). Here we show that 1,2-dithiolane probes, such as “TRFS” probes, are nonspecifically reduced by thiol reductants and redox-active proteins, and their cellular performance is barely affected by TrxR inhibition or knockout. Therefore, results of cellular imaging or inhibitor screening using 1,2-dithiolanes should not be interpreted as reflecting TrxR activity, and previous studies may need re-evaluation. To understand 1,2-dithiolanes’ complex behaviour, probe localisation, environment-dependent fluorescence, reduction-independent ring-opening polymerisation, and thiol-dependent cellular uptake must all be considered; particular caution is needed when co-applying thiophilic inhibitors. We present a general approach controlling against assay misinterpretation with reducible probes, to ensure future TrxR-targeted designs are robustly evaluated for selectivity, and to better orient future research. | |
| 700 | 1 | a Poczka, L4 aut |
| 700 | 1 | a Scholzen, KCu Karolinska Institutet4 aut |
| 700 | 1 | a Zeisel, L4 aut |
| 700 | 1 | a Maier, MS4 aut |
| 700 | 1 | a Busker, S4 aut |
| 700 | 1 | a Theisen, U4 aut |
| 700 | 1 | a Brandstadter, C4 aut |
| 700 | 1 | a Becker, K4 aut |
| 700 | 1 | a Arner, ESJu Karolinska Institutet4 aut |
| 700 | 1 | a Thorn-Seshold, J4 aut |
| 700 | 1 | a Thorn-Seshold, O4 aut |
| 710 | 2 | a Karolinska Institutet4 org |
| 773 | 0 | t Nature communicationsd : Springer Science and Business Media LLCg 13:1, s. 1754-q 13:1<1754-x 2041-1723 |
| 856 | 4 8 | u http://kipublications.ki.se/Default.aspx?queryparsed=id:149246184 |
| 856 | 4 8 | u https://doi.org/10.1038/s41467-022-29136-4 |
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