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Cyclometalated AuIII complexes for cysteine arylation in zinc finger protein domains: towards controlled reductive elimination

Wenzel, Margot, Bonsignore, Riccardo, Thomas, Sophie, Bourissou, Didier, Barone, Giampaolo and Casini, Angela 2019. Cyclometalated AuIII complexes for cysteine arylation in zinc finger protein domains: towards controlled reductive elimination. Chemistry - A European Journal 25 (32) , pp. 7628-7634. 10.1002/chem.201901535

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Abstract

With the aim of exploiting the use of organometallic species for the efficient modification of proteins through C‐atom transfer, we report here on the gold‐mediated cysteine arylation via reductive elimination process occurring from the reaction of cyclometalated Au(III) C^N complexes with a zinc finger peptide (Cys2His2 type). Among the four selected Au(III) cyclometallated compounds, the [Au(CCON)Cl2] complex featuring the 2‐benzoylpyridine (CCON) scaffold was identified as the most prone to reductive elimination and Cys arylation in buffered aqueous solution (pH 7.4) at 37°C by high‐resolution‐LC‐electrospray mass spectrometry. DFT and QM/MM studies allowed to propose a mechanism for the title reaction that is in line with the experimental results. Overall, the results provide new insights into the reactivity of cytotoxic organogold compounds with biologically important zinc finger domains and identify initial structure‐activity relationships to enable Au(III)‐catalysed reductive elimination in aqueous media.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Chemistry
Publisher: Wiley
ISSN: 0947-6539
Funders: EPSRC and European Union Horizon 2020
Date of First Compliant Deposit: 18 April 2019
Date of Acceptance: 16 April 2019
Last Modified: 18 Jul 2019 11:42
URI: http://orca.cf.ac.uk/id/eprint/121845

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