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Cyclic 5-membered d...
Cyclic 5-membered disulfides are not selective substrates of thioredoxin reductase, but are opened nonspecifically
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Felber, JG (author)
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Poczka, L (author)
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- Scholzen, KC (author)
- Karolinska Institutet
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Zeisel, L (author)
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Maier, MS (author)
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Busker, S (author)
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Theisen, U (author)
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Brandstadter, C (author)
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Becker, K (author)
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- Arner, ESJ (author)
- Karolinska Institutet
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Thorn-Seshold, J (author)
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Thorn-Seshold, O (author)
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(creator_code:org_t)
- 2022-04-01
- 2022
- English.
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In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1, s. 1754-
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https://doi.org/10.1...
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Abstract
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- 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.
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- art (subject category)
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- By the author/editor
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Felber, JG
-
Poczka, L
-
Scholzen, KC
-
Zeisel, L
-
Maier, MS
-
Busker, S
-
show more...
-
Theisen, U
-
Brandstadter, C
-
Becker, K
-
Arner, ESJ
-
Thorn-Seshold, J
-
Thorn-Seshold, O
-
show less...
- Articles in the publication
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Nature communica ...
- By the university
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Karolinska Institutet