Site-Selective Aryl Diazonium Installation onto Protein Surfaces at Neutral pH using a Maleimide-Functionalized Triazabutadiene.

azo compounds photolysis protecting groups protein modifications

Journal

Chembiochem : a European journal of chemical biology
ISSN: 1439-7633
Titre abrégé: Chembiochem
Pays: Germany
ID NLM: 100937360

Informations de publication

Date de publication:
15 08 2023
Historique:
revised: 01 06 2023
received: 20 04 2023
medline: 17 8 2023
pubmed: 13 6 2023
entrez: 13 6 2023
Statut: ppublish

Résumé

Aryl diazonium cations are versatile bioconjugation reagents due to their reactivity towards electron-rich aryl residues and secondary amines, but historically their usage has been hampered by both their short lifespan in aqueous solution and the harsh conditions required to generate them in situ. Triazabutadienes address many of these issues as they are stable enough to endure multiple-step chemical syntheses and can persist for several hours in aqueous solution, yet upon UV-exposure rapidly release aryl diazonium cations under biologically-relevant conditions. This paper describes the synthesis of a novel maleimide-functionalized triazabutadiene suitable for site-selectively installing aryl diazonium cations into proteins at neutral pH; we show reaction with this molecule and a surface-cysteine of a thiol disulfide oxidoreductase. Through photoactivation of the site-selectively installed triazabutadiene motifs, we generate aryl diazonium functionality, which we further derivatize via azo-bond formation to electron-rich aryl species, showcasing the potential utility of this strategy for the generation of photoswitches or protein-drug conjugates.

Identifiants

pubmed: 37311168
doi: 10.1002/cbic.202300313
doi:

Substances chimiques

Membrane Proteins 0
maleimide 2519R1UGP8
Maleimides 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

e202300313

Informations de copyright

© 2023 The Authors. ChemBioChem published by Wiley-VCH GmbH.

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Auteurs

Nicholas D J Yates (NDJ)

Department of Chemistry, University of York Heslington, York, YO10 5DD, UK.

Natasha E Hatton (NE)

Department of Chemistry, University of York Heslington, York, YO10 5DD, UK.

Martin A Fascione (MA)

Department of Chemistry, University of York Heslington, York, YO10 5DD, UK.

Alison Parkin (A)

Department of Chemistry, University of York Heslington, York, YO10 5DD, UK.

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