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Parallel evaluation of nucleophilic and electrophilic chemical probes for sulfenic acid: Reactivity, selectivity and biocompatibility
Cysteine sulfenic acids (Cys-SOH) are pivotal modifications in thiol-based redox signaling and central intermediates en route to disulfide and sulfinic acid states. A core mission in our lab is to develop bioorthogonal chemical tools with the potential to answer mechanistic questions involving cyste...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8321940/ https://www.ncbi.nlm.nih.gov/pubmed/34298464 http://dx.doi.org/10.1016/j.redox.2021.102072 |
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author | Shi, Yunlong Carroll, Kate S. |
author_facet | Shi, Yunlong Carroll, Kate S. |
author_sort | Shi, Yunlong |
collection | PubMed |
description | Cysteine sulfenic acids (Cys-SOH) are pivotal modifications in thiol-based redox signaling and central intermediates en route to disulfide and sulfinic acid states. A core mission in our lab is to develop bioorthogonal chemical tools with the potential to answer mechanistic questions involving cysteine oxidation. Our group, among others, has contributed to the development of nucleophilic chemical probes for detecting sulfenic acids in living cells. Recently, another class of Cys-SOH probes based on strained alkene and alkyne electrophiles has emerged. However, the use of different models of sulfenic acid and methodologies, has confounded clear comparison of these probes with respect to chemical reactivity, kinetics, and selectivity. Here, we perform a parallel evaluation of nucleophilic and electrophilic chemical probes for Cys-SOH. Among the key findings, we demonstrate that a probe for Cys-SOH based on the norbornene scaffold does not react with any of the validated sulfenic acid models in this study. Furthermore, we show that purported cross-reactivity of dimedone-like probes with electrophiles, like aldehydes and cyclic sulfenamides, is a not meaningful in a biological setting. In summary, nucleophilic probes remain the most viable tools for bioorthogonal detection of Cys-SOH. |
format | Online Article Text |
id | pubmed-8321940 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-83219402021-08-04 Parallel evaluation of nucleophilic and electrophilic chemical probes for sulfenic acid: Reactivity, selectivity and biocompatibility Shi, Yunlong Carroll, Kate S. Redox Biol Research Paper Cysteine sulfenic acids (Cys-SOH) are pivotal modifications in thiol-based redox signaling and central intermediates en route to disulfide and sulfinic acid states. A core mission in our lab is to develop bioorthogonal chemical tools with the potential to answer mechanistic questions involving cysteine oxidation. Our group, among others, has contributed to the development of nucleophilic chemical probes for detecting sulfenic acids in living cells. Recently, another class of Cys-SOH probes based on strained alkene and alkyne electrophiles has emerged. However, the use of different models of sulfenic acid and methodologies, has confounded clear comparison of these probes with respect to chemical reactivity, kinetics, and selectivity. Here, we perform a parallel evaluation of nucleophilic and electrophilic chemical probes for Cys-SOH. Among the key findings, we demonstrate that a probe for Cys-SOH based on the norbornene scaffold does not react with any of the validated sulfenic acid models in this study. Furthermore, we show that purported cross-reactivity of dimedone-like probes with electrophiles, like aldehydes and cyclic sulfenamides, is a not meaningful in a biological setting. In summary, nucleophilic probes remain the most viable tools for bioorthogonal detection of Cys-SOH. Elsevier 2021-07-16 /pmc/articles/PMC8321940/ /pubmed/34298464 http://dx.doi.org/10.1016/j.redox.2021.102072 Text en © 2021 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Research Paper Shi, Yunlong Carroll, Kate S. Parallel evaluation of nucleophilic and electrophilic chemical probes for sulfenic acid: Reactivity, selectivity and biocompatibility |
title | Parallel evaluation of nucleophilic and electrophilic chemical probes for sulfenic acid: Reactivity, selectivity and biocompatibility |
title_full | Parallel evaluation of nucleophilic and electrophilic chemical probes for sulfenic acid: Reactivity, selectivity and biocompatibility |
title_fullStr | Parallel evaluation of nucleophilic and electrophilic chemical probes for sulfenic acid: Reactivity, selectivity and biocompatibility |
title_full_unstemmed | Parallel evaluation of nucleophilic and electrophilic chemical probes for sulfenic acid: Reactivity, selectivity and biocompatibility |
title_short | Parallel evaluation of nucleophilic and electrophilic chemical probes for sulfenic acid: Reactivity, selectivity and biocompatibility |
title_sort | parallel evaluation of nucleophilic and electrophilic chemical probes for sulfenic acid: reactivity, selectivity and biocompatibility |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8321940/ https://www.ncbi.nlm.nih.gov/pubmed/34298464 http://dx.doi.org/10.1016/j.redox.2021.102072 |
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