ArticleAnalytical chemistry2025
Quantitative HILIC-Q-TOF-MS Analysis of Glycosaminoglycans and Non-reducing End Carbohydrate Biomarkers via Glycan Reductive Isotopic Labeling.
Article in Analytical chemistry, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed.
- CRISPR activation screens identify core protein-dependent regulation of heparan sulfate sulfation and ligand specificity.bioRxiv : the preprint server for biology · 2026Article
- Glycosaminoglycans in tissue regeneration: Insights into glycobiology and their biomedical application.Bioactive materials · 2026Review
- Sulfatase modifying factors control the timing of zebrafish convergence and extension morphogenesis.Nature communications · 2026Article
- HS6ST1 regulates acute myeloid leukemia chemotherapy resistance via TGF-β1 signaling.Research square · 2026Article
- Enhanced lysosomal exocytosis and altered growth factor signaling are associated with cartilage pathology in a model of mucopolysaccharidosis type IVA.Disease models & mechanisms · 2026Article
- A non-canonical EZH2/TRIM28 epigenetic axis drives heparan sulfate remodeling and melanoma metastasis.bioRxiv : the preprint server for biology · 2026Article
- Glycosaminoglycans and Their Role in Capillary Walls.Advances in experimental medicine and biology · 2026Review
- Mucin-typebioRxiv : the preprint server for biology · 2025Article
- Sulfatase modifying factors control the timing of zebrafish convergence and extension morphogenesis.bioRxiv : the preprint server for biology · 2025Article
- Article
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Authors and funding
13 authors.
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Abstract
Glycosaminoglycans (GAGs) are linear, heterogeneous polysaccharides expressed on all animal cells. Sulfated GAGs, including heparan sulfate (HS) and chondroitin/dermatan sulfate (CS/DS), are involved in numerous physiological and pathological processes; therefore, precise and robust analytical methods for their characterization are essential to correlate structure with function. In this study, we developed a method utilizing hydrophilic interaction liquid chromatography coupled with time-of-flight mass spectrometry (HILIC-Q-TOF-MS) and glycan reductive isotopic reducing end labeling (GRIL) for the quantitative compositional analysis of HS and CS/DS polysaccharides. Lyase-generated disaccharides and commercial standards were chemically tagged on the reducing end with aniline stable isotopes, thus enabling the absolute quantification of HS and CS/DS disaccharides in complex biological samples. In addition, we adapted this workflow, in conjunction with new synthetic carbohydrate standards, for the quantification of disease-specific non-reducing end (NRE) carbohydrate biomarkers that accumulate in patients with mucopolysaccharidoses (MPS), a subclass of lysosomal storage disorders. As a proof of concept, we applied this method to measure NRE biomarkers in patient-derived MPS IIIA and MPS IIID fibroblasts, as well as in cortex tissue from a murine model of MPS VII. Overall, this method demonstrates improved sensitivity compared to previous GRIL-LC/MS techniques and, importantly, avoids the use of ion-pairing reagents, which are undesirable in certain mass spectrometry instrumentation and contexts. By combining the benefits of HILIC separation with isotopic labeling, our approach offers a robust and accessible tool for the analysis of GAGs, paving the way for advancements in understanding GAG structure and function.
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