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  • Review Article
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Glycomics studies using sialic acid derivatization and mass spectrometry

Nature Reviews Chemistry volume 4, pages 229–242 (2020)Cite this article

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Abstract

Proteins can undergo glycosylation during and/or after translation to afford glycoconjugates, which are often secreted by a cell or populate cell surfaces. Changes in the glycan portion can have a strong influence on a glycoconjugate and are associated with a multitude of human pathologies. Of particular interest are sialylated glycoconjugates, which exist as constitutional isomers that differ in their linkages (α2,3, α2,6, α2,8 or α2,9) between sialic acids and their neighbouring monosaccharides. In general, mass spectrometry enables the rapid and sensitive characterization of glycosylation, but there are challenges specific to identifying and (relatively) quantifying sialic acid isomers. These challenges can be addressed using linkage-specific methodologies for sialic acid derivatization, after which mass spectrometry can enable product identification. This Review is concerned with the new and important derivatization approaches reported in the past decade, which have been implemented in various mass-spectrometry-glycomics workflows and have found clinical glycomics applications. The convenience and wide applicability of the approaches make them attractive for studies of sialylation in different types of glycoconjugate.

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Fig. 1: Prominent sialic acids and their variants.
Fig. 2: Sialylation is diverse and important in biology.
Fig. 3: Linkage-specific derivatization of sialic acids.
Fig. 4: MALDI-TOF-MS of released N-glycans after linkage-specific sialic acid derivatization.
Fig. 5: Solid-phase sample preparation aids analysis of protein N-glycosylation and O-glycosylation.
Fig. 6: Two-step linkage-specific sialic acid derivatization enables MS imaging of colorectal cancer.

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Acknowledgements

We thank S. Lippold and T. Pongracz for critically reading this manuscript.

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Authors and Affiliations

  1. Center for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, Netherlands

    Noortje de Haan & Manfred Wuhrer

  2. Laboratory of Bacterial Polysaccharides, Division of Bacterial, Parasitic and Allergenic Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD, USA

    Shuang Yang & John Cipollo

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  1. Noortje de Haan
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  2. Shuang Yang
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  4. Manfred Wuhrer
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All authors researched data and literature for the article and contributed to discussion of content and writing. All authors reviewed and edited the manuscript before submission. N.d.H. and M.W. wrote the first version of the manuscript. N.d.H. prepared the figures.

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Correspondence to Noortje de Haan.

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de Haan, N., Yang, S., Cipollo, J. et al. Glycomics studies using sialic acid derivatization and mass spectrometry. Nat Rev Chem 4, 229–242 (2020). https://doi.org/10.1038/s41570-020-0174-3

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