Mass spectrometry approaches to glycomic and glycoproteomic analyses
Open accessAbstract
Glycomic and glycoproteomic analyses involve the characterization of oligosaccharides (glycans) conjugated to proteins. Glycans are produced through a complicated nontemplate driven process involving the competition of enzymes that extend the nascent chain. The large diversity of structures, the variations in polarity of the individual saccharide residues, and the poor ionization efficiencies of glycans all conspire to make the analysis arguably much more difficult than any other biopolymer. Furthermore, the large number of glycoforms associated with a specific protein site makes it more difficult to characterize than any post-translational modification. Nonetheless, there have been significant progress, and advanced separation and mass spectrometry methods have been at its center and the main reason for the progress. While glycomic and glycoproteomic analyses are still typically available only through highly specialized laboratories, new software and workflow is making it more accessible. This review focuses on the role of mass spectrometry and separation methods in advancing glycomic and glycoproteomic analyses. It describes the current state of the field and progress toward making it more available to the larger scientific community.
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MALDI and ESI are soft ionisation techniques that now dominate in the MS field.
“Matrix-assisted laser desorption/ionisation (MALDI) and electrospray ionisation (ESI) are ‘soft ionisation' techniques, which now dominate in the MS field [142,145].”
From Glycoengineering Chinese hamster ovary cells: a short history (2021) · cites this paper as [142]
The “Ionization Considerations” section describes soft ionization techniques as normally used for glycan and glycopeptide analyses and says MALDI and ESI are the most widely used ionization methods in that context. It does not establish that they dominate the entire MS field, as the citing sentence claims. (LLM, conf=0.86)
Experimental — accuracy not yet measuredMass spectrometry-based techniques have dominated the glycomics and glycoproteomics fields for decades because of their high sensitivity and ability to characterise complex heterogeneous mixtures, especially when combined with upstream separation techniques such as liquid chromatography.
“Mass spectrometry (MS)-based techniques, the experimental workflow for which is outlined in Figure 3, have dominated the glycomics and glycoproteomics fields for decades because of its high sensitivity and ability to characterise complex heterogeneous mixtures, especially when combined with upstream separation techniques such as liquid chromatography [142].”
From Glycoengineering Chinese hamster ovary cells: a short history (2021) · cites this paper as [142]
The Introduction (page unavailable) says MS has been central to glycomic and glycoproteomic analysis and describes its use with HPLC and UPLC. The instrumentation section (page unavailable) supports the sensitivity claim, while the separation-methods section explains why LC helps analyze heterogeneous glycan samples. The copy does not establish that MS dominated both fields for decades. (LLM, conf=0.82)
Experimental — accuracy not yet measured
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Percentages, sums and reported differences re-computed from the paper’s own numbers.
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Cites
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Analysis of glycans derived from glycoconjugates by capillary electrophoresis‐mass spectrometry
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- Authors
- Ruhaak, L. R., Xu, G., Li, Q., Goonatilleke, E., & Lebrilla, C. B.
- Affiliations
- Leiden University Medical Center (NL)
- University of California, Davis (US)
- Corresponding author
- Lebrilla, Carlito B.
- Venue
- Chemical Reviews
- Publisher
- American Chemical Society (ACS)
- Published
- 2018-03-19
- Volume
- 118
- Issue
- 17
- Pages
- 7886-7930
- ISSN
- 0009-2665 (ISSN-L)
- 1520-6890
- PMC
- PMC7757723
- OpenAlex
- W2789682399
- Cited by
- 395
- References
- 6
- Citations by year
- 2026: 32 · 2025: 44 · 2024: 48 · 2023: 40 · 2022: 50 · 2021: 77 · 2020: 50 · 2019: 45 · 2018: 8
- FWCI
- 4.41
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Chemical Reviews (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Leiden Repository (Leiden University) (submittedVersion)
- Funders
- National Institute of Child Health and Human Development (R01 HD061923)
- National Center for Complementary and Integrative Health (RO1 AT008759)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Glycosylation and Glycoproteins Research
- Physical Sciences › Chemistry › Spectroscopy › Mass Spectrometry Techniques and Applications
- Physical Sciences › Chemistry › Spectroscopy › Advanced Proteomics Techniques and Applications
- Keywords
- glycomics, glycoproteomics, glycans, oligosaccharides, glycan analysis, glycoforms, post-translational modification, glycan separation, mass spectrometry workflow, glycan characterization
- MeSH terms
- Glycoproteins, Glycosylation, Polysaccharides, Protein Processing, Post-Translational, Mass Spectrometry, Proteomics, Glycomics
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