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Red-light-induced cysteine modifications suitable for protein labeling

Red-light-induced cysteine modifications suitable for protein labeling
Red-light-induced cysteine modifications suitable for protein labeling
The naturally low abundance of cysteine in proteins, combined with its propensity to undergo thiol–ene reactions, makes it a preferred amino acid for various bioconjugations. However, most of these methods rely on the use of UV radiation, radical initiators, or heavy-metal-based photocatalysts, which limits their applicability in complex biological environments. Herein, we report a photocatalyzed thiol–ene radical reaction that overcomes these limitations by employing a porphyrin-based photocatalyst and low-energy red light. This method operates under mild reaction conditions and can be expanded to a cysteinyl desulfurization reaction. As this approach proceeds in aqueous media and facilitates selective transformations of both simple free cysteine and cysteine residues within complex protein, it significantly expands the existing toolbox for cysteine bioconjugation.
bioconjugation, cysteine, photocatalysis, porphyrin, proteins, red light, thiol-ene reaction
2694-247X
Wdowik, Tomasz
7460f841-ab16-4621-bfc4-8fc6c97cdc29
Fedorov, Egor
0e43da80-393c-41e8-83de-eb555019cde5
Ho, Tina-Thien
6e29e0a9-751e-466e-8321-49f0325fccb9
Duriez, Patrick
4cf499bc-007a-43b3-b180-d6e5dc3d151b
Stulz, Eugen
9a6c04cf-32ca-442b-9281-bbf3d23c622d
Gryko, Dorota
67e6fcd5-0d54-4a5d-a93b-61d74251b661
Wdowik, Tomasz
7460f841-ab16-4621-bfc4-8fc6c97cdc29
Fedorov, Egor
0e43da80-393c-41e8-83de-eb555019cde5
Ho, Tina-Thien
6e29e0a9-751e-466e-8321-49f0325fccb9
Duriez, Patrick
4cf499bc-007a-43b3-b180-d6e5dc3d151b
Stulz, Eugen
9a6c04cf-32ca-442b-9281-bbf3d23c622d
Gryko, Dorota
67e6fcd5-0d54-4a5d-a93b-61d74251b661

Wdowik, Tomasz, Fedorov, Egor, Ho, Tina-Thien, Duriez, Patrick, Stulz, Eugen and Gryko, Dorota (2025) Red-light-induced cysteine modifications suitable for protein labeling. ACS Organic and Inorganic Au. (doi:10.1021/acsorginorgau.5c00025).

Record type: Article

Abstract

The naturally low abundance of cysteine in proteins, combined with its propensity to undergo thiol–ene reactions, makes it a preferred amino acid for various bioconjugations. However, most of these methods rely on the use of UV radiation, radical initiators, or heavy-metal-based photocatalysts, which limits their applicability in complex biological environments. Herein, we report a photocatalyzed thiol–ene radical reaction that overcomes these limitations by employing a porphyrin-based photocatalyst and low-energy red light. This method operates under mild reaction conditions and can be expanded to a cysteinyl desulfurization reaction. As this approach proceeds in aqueous media and facilitates selective transformations of both simple free cysteine and cysteine residues within complex protein, it significantly expands the existing toolbox for cysteine bioconjugation.

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Accepted/In Press date: 3 April 2025
e-pub ahead of print date: 9 April 2025
Published date: 6 August 2025
Keywords: bioconjugation, cysteine, photocatalysis, porphyrin, proteins, red light, thiol-ene reaction

Identifiers

Local EPrints ID: 501540
URI: http://eprints.soton.ac.uk/id/eprint/501540
ISSN: 2694-247X
PURE UUID: 4aa5b510-0389-4b4d-bd08-57dfc1d1fa69
ORCID for Tina-Thien Ho: ORCID iD orcid.org/0000-0002-0576-8428
ORCID for Patrick Duriez: ORCID iD orcid.org/0000-0003-1814-2552
ORCID for Eugen Stulz: ORCID iD orcid.org/0000-0002-5302-2276

Catalogue record

Date deposited: 03 Jun 2025 16:56
Last modified: 03 Sep 2025 01:41

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Contributors

Author: Tomasz Wdowik
Author: Egor Fedorov
Author: Tina-Thien Ho ORCID iD
Author: Patrick Duriez ORCID iD
Author: Eugen Stulz ORCID iD
Author: Dorota Gryko

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