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Article Dans Une Revue Chemistry - A European Journal Année : 2024

Gold‐promoted biocompatible selenium arylation of small molecules, peptides and proteins

Résumé

Abstract A low pKa (5.2), high polarizable volume (3.8 Å), and proneness to oxidation under ambient conditions make selenocysteine (Sec, U) a unique, natural reactive handle present in most organisms across all domains of life. Sec modification still has untapped potential for site‐selective protein modification and probing. Herein we demonstrate the use of a cyclometalated gold(III) compound, [Au(bnpy)Cl 2 ], in the arylation of diselenides of biological significance, with a scope covering small molecule models, peptides, and proteins using a combination of multinuclear NMR (including 77 Se NMR), and LC–MS. Diphenyl diselenide (Ph−Se) 2 and selenocystine, (Sec) 2 , were used for reaction optimization. This approach allowed us to demonstrate that an excess of diselenide (Au/Se−Se) and an increasing water percentage in the reaction media enhance both the conversion and kinetics of the C−Se coupling reaction, a combination that makes the reaction biocompatible. The C−Se coupling reaction was also shown to happen for the diselenide analogue of the cyclic peptide vasopressin ((Se−Se)‐AVP), and the Bos taurus glutathione peroxidase (GPx1) enzyme in ammonium acetate (2 mM, pH=7.0). The reaction mechanism, studied by DFT revealed a redox‐based mechanism where the C−Se coupling is enabled by the reductive elimination of the cyclometalated Au(III) species into Au(I).
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Dates et versions

hal-04425725 , version 1 (30-04-2024)

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Douglas Nakahata, Ioannis Kanavos, Maria Zubiria-Ulacia, Alex Inague, Luca Salassa, et al.. Gold‐promoted biocompatible selenium arylation of small molecules, peptides and proteins. Chemistry - A European Journal, 2024, 30 (15), pp.e202304050. ⟨10.1002/chem.202304050⟩. ⟨hal-04425725⟩
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