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Article
Azabicyclic vinyl sulfones for residue-specific dual protein labelling
Author/s | Gil de Montes Rojas, Enrique
Jiménez Moreno, Ester Oliveira, Bruno L. Navo, Claudio D. Robina Ramírez, Inmaculada Moreno Vargas, Antonio José |
Department | Universidad de Sevilla. Departamento de Química Orgánica |
Publication Date | 2019 |
Deposit Date | 2019-07-09 |
Published in |
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Abstract | We have developed [2.2.1]azabicyclic vinyl sulfone reagents that simultaneously enable cysteine-selective protein modification and introduce a handle for further bioorthogonal ligation. The reaction is fast and selective ... We have developed [2.2.1]azabicyclic vinyl sulfone reagents that simultaneously enable cysteine-selective protein modification and introduce a handle for further bioorthogonal ligation. The reaction is fast and selective for cysteine relative to other amino acids that have nucleophilic side-chains, and the formed products are stable in human plasma and are moderately resistant to retro Diels–Alder degradation reactions. A model biotinylated [2.2.1]azabicyclic vinyl sulfone reagent was shown to efficiently label two cysteine-tagged proteins, ubiquitin and C2Am, under mild conditions (1–5 equiv. of reagent in NaPi pH 7.0, room temperature, 30 min). The resulting thioether-linked conjugates were stable and retained the native activity of the proteins. Finally, the dienophile present in the azabicyclic moiety on a functionalised C2Am protein could be fluorescently labelled through an inverse electron demand Diels–Alder reaction in cells to allow selective apoptosis imaging. The combined advantages of directness, site-specificity and easy preparation mean [2.2.1]azabicyclic vinyl sulfones can be used for residue-specific dual protein labelling/construction strategies with minimal perturbation of native function based simply on the attachment of an [2.2.1]azabicyclic moiety to cysteine. |
Project ID. | CTQ2016-77270-R
CTQ2015-70524-R PP2017- 8144 RYC-2013-14706 |
Citation | Gil de Montes Rojas, E., Jiménez Moreno, E., Oliveira, B.L., Navo, .D., Robina Ramírez, I. y Moreno Vargas, A.J. (2019). Azabicyclic vinyl sulfones for residue-specific dual protein labelling. Chemical Science, 10 (6), 4515-4522. |
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