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Ion mobility-tandem mass spectrometry of mucin-type O-glycans

Bechtella, L.; Chunsheng, J.; Fentker, K.; Ertürk, G.R.; Safferthal, M.; Polewski, L.; Götze, M., Graeber, S.Y.; Vos, G.M, Struwe, W.B.; Mall, M.A.; Mertins, P., Karlsson, N.G.; Pagel, K.* – 2024

The dense O-glycosylation of mucins plays an important role in the defensive properties of the mucus hydrogel. Aberrant glycosylation is often correlated with inflammation and pathology such as COPD, cancer, and Crohn’s disease. The inherent complexity of glycans and the diversity in the O-core structure constitute fundamental challenges for the analysis of mucin-type O-glycans. Due to coexistence of multiple isomers, multidimensional workflows such as LC-MS are required. To separate the highly polar carbohydrates, porous graphitized carbon is often used as a stationary phase. However, LC-MS workflows are time-consuming and lack reproducibility. Here we present a rapid alternative for separating and identifying O-glycans released from mucins based on trapped ion mobility mass spectrometry. Compared to established LC-MS, the acquisition time is reduced from an hour to two minutes. To test the validity, the developed workflow was applied to sputum samples from cystic fibrosis patients to map O-glycosylation features associated with disease.

Title
Ion mobility-tandem mass spectrometry of mucin-type O-glycans
Author
Bechtella, L.; Chunsheng, J.; Fentker, K.; Ertürk, G.R.; Safferthal, M.; Polewski, L.; Götze, M., Graeber, S.Y.; Vos, G.M, Struwe, W.B.; Mall, M.A.; Mertins, P., Karlsson, N.G.; Pagel, K.*
Date
2024-03
Citation
Nat. Commun. 2024, https://doi.org/10.1038/s41467-024-46825-4
Type
Text

The dense O-glycosylation of mucins plays an important role in the defensive properties of the mucus hydrogel. Aberrant glycosylation is often correlated with inflammation and pathology such as COPD, cancer, and Crohn’s disease. The inherent complexity of glycans and the diversity in the O-core structure constitute fundamental challenges for the analysis of mucin-type O-glycans. Due to coexistence of multiple isomers, multidimensional workflows such as LC-MS are required. To separate the highly polar carbohydrates, porous graphitized carbon is often used as a stationary phase. However, LC-MS workflows are time-consuming and lack reproducibility. Here we present a rapid alternative for separating and identifying O-glycans released from mucins based on trapped ion mobility mass spectrometry. Compared to established LC-MS, the acquisition time is reduced from an hour to two minutes. To test the validity, the developed workflow was applied to sputum samples from cystic fibrosis patients to map O-glycosylation features associated with disease.

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