Targeted Annotation of S-Sulfonylated Peptides by Selective Infrared Multiphoton Dissociation Mass Spectrometry
| Autor: | Phillip J. McClory, Brent R. Martin, Nicholas B. Borotto, Kristina Håkansson |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Chromatography Chemistry Infrared Rays Oxidative phosphorylation Mass spectrometry Tandem mass spectrometry Combinatorial chemistry Dissociation (chemistry) Mass Spectrometry Article Analytical Chemistry Absorbance 03 medical and health sciences 030104 developmental biology Proteome Infrared multiphoton dissociation Cysteine Peptides Oxidation-Reduction Protein Processing Post-Translational |
| Zdroj: | Analytical chemistry. 89(16) |
| ISSN: | 1520-6882 |
| Popis: | Protein S-sulfinylation (R-SO2−) and S-sulfonylation (R-SO3−) are irreversible oxidative post-translational modifications of cysteine residues. Greater than 5% of cysteines are reported to occupy these higher oxidation states, which effectively inactivate the corresponding thiols and alter the electronic and physical properties of modified proteins. Such higher oxidation states are reached after excessive exposure to cellular oxidants, and accumulate across different disease states. Despite widespread and functionally relevant cysteine oxidation across the proteome, there are currently no robust methods to profile higher order cysteine oxidation. Traditional data-dependent liquid chromatography/tandem mass spectrometry (LC/MS/MS) methods generally miss low occupancy modifications in complex analyses. Here, we present a data-independent acquisition (DIA) LC/MS-based approach, leveraging the high IR absorbance of sulfoxides at 10.6 μm, for selective dissociation and discovery of S-sulfonated peptides. Across peptide standards and protein digests, we demonstrate selective infrared multiphoton dissociation (IRMPD) of S-sulfonated peptides in the background of unmodified peptides. This selective DIA IRMPD LC/MS-based approach allows identification and annotation of S-sulfonated peptides across complex mixtures while providing sufficient sequence information to localize the modification site. |
| Databáze: | OpenAIRE |
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