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Hybrid mass spectrometry approaches in glycoprotein analysis and their usage in scoring biosimilarity

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  • Yang Yang

    (Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, University of Utrecht
    Netherlands Proteomics Center)

  • Fan Liu

    (Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, University of Utrecht
    Netherlands Proteomics Center)

  • Vojtech Franc

    (Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, University of Utrecht
    Netherlands Proteomics Center)

  • Liem Andhyk Halim

    (Utrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht University)

  • Huub Schellekens

    (Utrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht University)

  • Albert J. R. Heck

    (Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, University of Utrecht
    Netherlands Proteomics Center)

Abstract

Many biopharmaceutical products exhibit extensive structural micro-heterogeneity due to an array of co-occurring post-translational modifications. These modifications often effect the functionality of the product and therefore need to be characterized in detail. Here, we present an integrative approach, combining two advanced mass spectrometry-based methods, high-resolution native mass spectrometry and middle-down proteomics, to analyse this micro-heterogeneity. Taking human erythropoietin and the human plasma properdin as model systems, we demonstrate that this strategy bridges the gap between peptide- and protein-based mass spectrometry platforms, providing the most complete profiling of glycoproteins. Integration of the two methods enabled the discovery of three undescribed C-glycosylation sites on properdin, and revealed in addition unexpected heterogeneity in occupancies of C-mannosylation. Furthermore, using various sources of erythropoietin we define and demonstrate the usage of a biosimilarity score to quantitatively assess structural similarity, which would also be beneficial for profiling other therapeutic proteins and even plasma protein biomarkers.

Suggested Citation

  • Yang Yang & Fan Liu & Vojtech Franc & Liem Andhyk Halim & Huub Schellekens & Albert J. R. Heck, 2016. "Hybrid mass spectrometry approaches in glycoprotein analysis and their usage in scoring biosimilarity," Nature Communications, Nature, vol. 7(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms13397
    DOI: 10.1038/ncomms13397
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    Cited by:

    1. Luis F. Schachner & Christopher Mullen & Wilson Phung & Joshua D. Hinkle & Michelle Irwin Beardsley & Tracy Bentley & Peter Day & Christina Tsai & Siddharth Sukumaran & Tomasz Baginski & Danielle DiCa, 2024. "Exposing the molecular heterogeneity of glycosylated biotherapeutics," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    2. Luke J. Dowman & Sameer S. Kulkarni & Juan V. Alegre-Requena & Andrew M. Giltrap & Alexander R. Norman & Ashish Sharma & Liliana C. Gallegos & Angus S. Mackay & Adarshi P. Welegedara & Emma E. Watson , 2022. "Site-selective photocatalytic functionalization of peptides and proteins at selenocysteine," Nature Communications, Nature, vol. 13(1), pages 1-12, December.

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