Yates, Nicholas David James, Hatton, Natasha Emily, Fascione, Martin Anthony orcid.org/0000-0002-0066-4419 et al. (1 more author) (2023) Site-Selective Aryl Diazonium Installation onto Protein Surfaces at Neutral pH using a Maleimide-Functionalized Triazabutadiene. Chembiochem. e202300313. ISSN 1439-7633
Abstract
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 photo switches or protein-drug conjugates.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2023 The Authors. |
Dates: |
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Institution: | The University of York |
Academic Units: | The University of York > Faculty of Sciences (York) > Chemistry (York) |
Funding Information: | Funder Grant number EUROPEAN COMMISSION 101045109 / EP/X027724/1 EUROPEAN COMMISSION 101044024 |
Depositing User: | Pure (York) |
Date Deposited: | 12 Jul 2023 14:40 |
Last Modified: | 27 Dec 2024 00:24 |
Published Version: | https://doi.org/10.1002/cbic.202300313 |
Status: | Published |
Refereed: | Yes |
Identification Number: | 10.1002/cbic.202300313 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:201519 |