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 (2016). Chemoselective synthesis and analysis of naturally occurring phosphorylated cysteine peptides. Nature communications, 7, p. 12703. Nature Publishing Group 10.1038/ncomms12703

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Biochemistry and Molecular Medicine

UniBE Contributor:

Jeckelmann, Jean-Marc

Subjects:

500 Science > 570 Life sciences; biology
600 Technology > 610 Medicine & health

ISSN:

2041-1723

Publisher:

Nature Publishing Group

Language:

English

Submitter:

Barbara Järmann-Bangerter

Date Deposited:

04 Jun 2018 15:50

Last Modified:

10 Jun 2018 02:22

Publisher DOI:

10.1038/ncomms12703

PubMed ID:

27586301

BORIS DOI:

10.7892/boris.111401

URI:

https://boris.unibe.ch/id/eprint/111401

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