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Chemoselective synthesis and analysis of naturally occurring phosphorylated cysteine peptides
In contrast to protein O-phosphorylation, studying the function of the less frequent N- and S-phosphorylation events have lagged behind because they have chemical features that prevent their manipulation through standard synthetic and analytical methods. Here we report on the development of a chemos...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5025809/ https://www.ncbi.nlm.nih.gov/pubmed/27586301 http://dx.doi.org/10.1038/ncomms12703 |
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author | Bertran-Vicente, Jordi Penkert, Martin Nieto-Garcia, Olaia Jeckelmann, Jean-Marc Schmieder, Peter Krause, Eberhard Hackenberger, Christian P. R. |
author_facet | Bertran-Vicente, Jordi Penkert, Martin Nieto-Garcia, Olaia Jeckelmann, Jean-Marc Schmieder, Peter Krause, Eberhard Hackenberger, Christian P. R. |
author_sort | Bertran-Vicente, Jordi |
collection | PubMed |
description | In contrast to protein O-phosphorylation, studying the function of the less frequent N- and S-phosphorylation events have lagged behind because they have chemical features that prevent their manipulation through standard synthetic and analytical methods. Here we report on the development of a chemoselective synthetic method to phosphorylate Cys side-chains in unprotected peptides. This approach makes use of a reaction between nucleophilic phosphites and electrophilic disulfides accessible by standard methods. We achieve the stereochemically defined phosphorylation of a Cys residue and verify the modification using electron-transfer higher-energy dissociation (EThcD) mass spectrometry. To demonstrate the use of the approach in resolving biological questions, we identify an endogenous Cys phosphorylation site in IICB(Glc), which is known to be involved in the carbohydrate uptake from the bacterial phosphotransferase system (PTS). This new chemical and analytical approach finally allows further investigating the functions and significance of Cys phosphorylation in a wide range of crucial cellular processes. |
format | Online Article Text |
id | pubmed-5025809 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-50258092016-09-23 Chemoselective synthesis and analysis of naturally occurring phosphorylated cysteine peptides Bertran-Vicente, Jordi Penkert, Martin Nieto-Garcia, Olaia Jeckelmann, Jean-Marc Schmieder, Peter Krause, Eberhard Hackenberger, Christian P. R. Nat Commun Article In contrast to protein O-phosphorylation, studying the function of the less frequent N- and S-phosphorylation events have lagged behind because they have chemical features that prevent their manipulation through standard synthetic and analytical methods. Here we report on the development of a chemoselective synthetic method to phosphorylate Cys side-chains in unprotected peptides. This approach makes use of a reaction between nucleophilic phosphites and electrophilic disulfides accessible by standard methods. We achieve the stereochemically defined phosphorylation of a Cys residue and verify the modification using electron-transfer higher-energy dissociation (EThcD) mass spectrometry. To demonstrate the use of the approach in resolving biological questions, we identify an endogenous Cys phosphorylation site in IICB(Glc), which is known to be involved in the carbohydrate uptake from the bacterial phosphotransferase system (PTS). This new chemical and analytical approach finally allows further investigating the functions and significance of Cys phosphorylation in a wide range of crucial cellular processes. Nature Publishing Group 2016-09-02 /pmc/articles/PMC5025809/ /pubmed/27586301 http://dx.doi.org/10.1038/ncomms12703 Text en Copyright © 2016, The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Article Bertran-Vicente, Jordi Penkert, Martin Nieto-Garcia, Olaia Jeckelmann, Jean-Marc Schmieder, Peter Krause, Eberhard Hackenberger, Christian P. R. Chemoselective synthesis and analysis of naturally occurring phosphorylated cysteine peptides |
title | Chemoselective synthesis and analysis of naturally occurring phosphorylated cysteine peptides |
title_full | Chemoselective synthesis and analysis of naturally occurring phosphorylated cysteine peptides |
title_fullStr | Chemoselective synthesis and analysis of naturally occurring phosphorylated cysteine peptides |
title_full_unstemmed | Chemoselective synthesis and analysis of naturally occurring phosphorylated cysteine peptides |
title_short | Chemoselective synthesis and analysis of naturally occurring phosphorylated cysteine peptides |
title_sort | chemoselective synthesis and analysis of naturally occurring phosphorylated cysteine peptides |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5025809/ https://www.ncbi.nlm.nih.gov/pubmed/27586301 http://dx.doi.org/10.1038/ncomms12703 |
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