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Cyclic 5-membered d...
Cyclic 5-membered disulfides are not selective substrates of thioredoxin reductase, but are opened nonspecifically
- Artikel/kapitelEngelska2022
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2022-04-01
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Springer Science and Business Media LLC,2022
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LIBRIS-ID:oai:prod.swepub.kib.ki.se:149246184
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http://kipublications.ki.se/Default.aspx?queryparsed=id:149246184URI
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https://doi.org/10.1038/s41467-022-29136-4DOI
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Språk:engelska
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Sammanfattning på:engelska
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Ämneskategori:art swepub-publicationtype
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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.
Biuppslag (personer, institutioner, konferenser, titlar ...)
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Poczka, L
(författare)
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Scholzen, KCKarolinska Institutet
(författare)
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Zeisel, L
(författare)
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Maier, MS
(författare)
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Busker, S
(författare)
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Theisen, U
(författare)
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Brandstadter, C
(författare)
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Becker, K
(författare)
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Arner, ESJKarolinska Institutet
(författare)
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Thorn-Seshold, J
(författare)
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Thorn-Seshold, O
(författare)
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Karolinska Institutet
(creator_code:org_t)
Sammanhörande titlar
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Ingår i:Nature communications: Springer Science and Business Media LLC13:1, s. 1754-2041-1723
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Felber, JG
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Poczka, L
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Scholzen, KC
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Zeisel, L
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Maier, MS
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Busker, S
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visa fler...
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Theisen, U
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Brandstadter, C
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Becker, K
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Arner, ESJ
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Thorn-Seshold, J
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Thorn-Seshold, O
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visa färre...
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Nature communica ...
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Karolinska Institutet