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Updated: Mar 10, 2026

A Mass Spectrometry-Based Proteomics Approach for Global and High-Confidence Protein R-Methylation Analysis
Published on: April 28, 2022
Dual reductive/oxidative electrochemistry/liquid chromatography/mass spectrometry: Towards peptide and protein
Lars Büter1, Lisa M Frensemeier2, Martin Vogel2
1Westfälische Wilhelms-Universität Münster, Institut für Anorganische und Analytische Chemie, Corrensstraße 30, 48149 Münster, Germany; Westfälische Wilhelms-Universität Münster, NRW Graduate School of Chemistry, Wilhelm-Klemm-Straße 10, 48149 Münster, Germany.
Abstract:
A new hyphenated technique based on on-line dual (oxidative and reductive) electrochemistry coupled to liquid chromatography and high resolution electrospray mass spectrometry is presented. Two liquid streams are combined, with one containing a disulfide, which is reduced to the respective thiol in an electrochemical cell based on a titanium working electrode. The other stream contains phenol, which is electrochemically activated to benzoquinone on a boron-doped diamond working electrode. Upon combination of the two streams, a Michael addition takes places, leading to the covalent coupling of thiol to quinone. In continuous flow, the reaction mixture is transferred into an injection valve and the products are separated by reversed phase liquid chromatography and detected by electrospray-high resolution mass spectrometry. Proof of concept is demonstrated for low molecular mass disulfides and peptides, but further optimization will be required in future work to achieve efficient protein labelling.
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