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Azabicyclic vinyl sulfones for residue-specific dual protein labelling
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,...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Royal Society of Chemistry
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6482879/ https://www.ncbi.nlm.nih.gov/pubmed/31057781 http://dx.doi.org/10.1039/c9sc00125e |
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author | Gil de Montes, Enrique Jiménez-Moreno, Ester Oliveira, Bruno L. Navo, Claudio D. Cal, Pedro M. S. D. Jiménez-Osés, Gonzalo Robina, Inmaculada Moreno-Vargas, Antonio J. Bernardes, Gonçalo J. L. |
author_facet | Gil de Montes, Enrique Jiménez-Moreno, Ester Oliveira, Bruno L. Navo, Claudio D. Cal, Pedro M. S. D. Jiménez-Osés, Gonzalo Robina, Inmaculada Moreno-Vargas, Antonio J. Bernardes, Gonçalo J. L. |
author_sort | Gil de Montes, Enrique |
collection | PubMed |
description | 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 NaP(i) 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. |
format | Online Article Text |
id | pubmed-6482879 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Royal Society of Chemistry |
record_format | MEDLINE/PubMed |
spelling | pubmed-64828792019-05-03 Azabicyclic vinyl sulfones for residue-specific dual protein labelling Gil de Montes, Enrique Jiménez-Moreno, Ester Oliveira, Bruno L. Navo, Claudio D. Cal, Pedro M. S. D. Jiménez-Osés, Gonzalo Robina, Inmaculada Moreno-Vargas, Antonio J. Bernardes, Gonçalo J. L. Chem Sci Chemistry 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 NaP(i) 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. Royal Society of Chemistry 2019-03-18 /pmc/articles/PMC6482879/ /pubmed/31057781 http://dx.doi.org/10.1039/c9sc00125e Text en This journal is © The Royal Society of Chemistry 2019 http://creativecommons.org/licenses/by/3.0/ This article is freely available. This article is licensed under a Creative Commons Attribution 3.0 Unported Licence (CC BY 3.0) |
spellingShingle | Chemistry Gil de Montes, Enrique Jiménez-Moreno, Ester Oliveira, Bruno L. Navo, Claudio D. Cal, Pedro M. S. D. Jiménez-Osés, Gonzalo Robina, Inmaculada Moreno-Vargas, Antonio J. Bernardes, Gonçalo J. L. Azabicyclic vinyl sulfones for residue-specific dual protein labelling |
title | Azabicyclic vinyl sulfones for residue-specific dual protein labelling
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title_full | Azabicyclic vinyl sulfones for residue-specific dual protein labelling
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title_fullStr | Azabicyclic vinyl sulfones for residue-specific dual protein labelling
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title_full_unstemmed | Azabicyclic vinyl sulfones for residue-specific dual protein labelling
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title_short | Azabicyclic vinyl sulfones for residue-specific dual protein labelling
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title_sort | azabicyclic vinyl sulfones for residue-specific dual protein labelling |
topic | Chemistry |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6482879/ https://www.ncbi.nlm.nih.gov/pubmed/31057781 http://dx.doi.org/10.1039/c9sc00125e |
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