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

Author

Listed:
  • Leïla Bechtella

    (Freie Universität Berlin
    Fritz Haber Institute of the Max Planck Society)

  • Jin Chunsheng

    (University of Gothenburg)

  • Kerstin Fentker

    (Freie Universität Berlin
    Max Delbrück Center for Molecular Medicine)

  • Güney R. Ertürk

    (Freie Universität Berlin)

  • Marc Safferthal

    (Freie Universität Berlin
    Fritz Haber Institute of the Max Planck Society)

  • Łukasz Polewski

    (Freie Universität Berlin
    Fritz Haber Institute of the Max Planck Society)

  • Michael Götze

    (Freie Universität Berlin
    Fritz Haber Institute of the Max Planck Society)

  • Simon Y. Graeber

    (corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin
    German Center for Lung Research (DZL)
    Berlin Institute of Health at Charité – Universitätsmedizin Berlin)

  • Gaël M. Vos

    (Freie Universität Berlin
    Fritz Haber Institute of the Max Planck Society)

  • Weston B. Struwe

    (University of Oxford
    University of Oxford)

  • Marcus A. Mall

    (corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin
    German Center for Lung Research (DZL)
    Berlin Institute of Health at Charité – Universitätsmedizin Berlin)

  • Philipp Mertins

    (Max Delbrück Center for Molecular Medicine
    Berlin Institute of Health)

  • Niclas G. Karlsson

    (University of Gothenburg
    Oslo Metropolitan University)

  • Kevin Pagel

    (Freie Universität Berlin
    Fritz Haber Institute of the Max Planck Society)

Abstract

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.

Suggested Citation

  • Leïla Bechtella & Jin Chunsheng & Kerstin Fentker & Güney R. Ertürk & Marc Safferthal & Łukasz Polewski & Michael Götze & Simon Y. Graeber & Gaël M. Vos & Weston B. Struwe & Marcus A. Mall & Philipp M, 2024. "Ion mobility-tandem mass spectrometry of mucin-type O-glycans," Nature Communications, Nature, vol. 15(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-46825-4
    DOI: 10.1038/s41467-024-46825-4
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    References listed on IDEAS

    as
    1. Gaёl M. Vos & Kevin C. Hooijschuur & Zeshi Li & John Fjeldsted & Christian Klein & Robert P. Vries & Javier Sastre Toraño & Geert-Jan Boons, 2023. "Sialic acid O-acetylation patterns and glycosidic linkage type determination by ion mobility-mass spectrometry," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    2. J. Hofmann & H. S. Hahm & P. H. Seeberger & K. Pagel, 2015. "Identification of carbohydrate anomers using ion mobility–mass spectrometry," Nature, Nature, vol. 526(7572), pages 241-244, October.
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