Identification of Glycosaminoglycans with MS-Based Analytical Techniques

Glycosaminoglycans (GAGs) are linear anionic polysaccharides that play many important biological functions such as cell-signaling, cell recognition, inflammation, angiogenesis on the cell surface¹. However, the structural heterogeneity of GAGs and their low abundance in biological systems have made their analysis difficult². There has been much interest over the decades to characterize the structures of GAGs to better understand their function and roles in diseases, and to develop GAG-based biomimetics and biotherapeutics^{3, 4}.

Mass spectrometry (MS) has proven to be a powerful tool for obtaining detailed structural information for GAGs. This presentation will focus on the application of Fourier transform-ion cyclotron resonance (FT-ICR) MS to GAG analysis, taking advantage of its high resolution, sensitivity, and accuracy, especially for low-abundance samples². Chemometric approaches have been employed to help interpret complex MS datasets and have been used to differentiate isomeric structures from each other, and identify GAG related biomarkers tied to diseases⁵. Examples will be shown of the analysis of complex mixtures of fully intact GAGs from biological media using capillary zone electrophoresis-mass spectrometry (CZE-MS)⁶.

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2.         Pepi, L. E.;  Sanderson, P.;  Stickney, M.; Amster, I. J., Developments in Mass Spectrometry for Glycosaminoglycan Analysis: A Review. Molecular & cellular proteomics : MCP 2021, 20, 100025.

3.         Zaia, J., Mass spectrometry of oligosaccharides. 2004, 23 (3), 161-227.

4.         Song, Y.;  Zhang, F.; Linhardt, R. J., Analysis of the glycosaminoglycan chains of proteoglycans. Journal of Histochemistry & Cytochemistry 2021, 69 (2), 121-135.

5.         Leach Iii, F. E.;  Wolff, J. J.;  Xiao, Z.;  Ly, M.;  Laremore, T. N.;  Arungundram, S.;  Al-Mafraji, K.;  Venot, A.;  Boons, G.-J.; Linhardt, R. J., Negative electron transfer dissociation Fourier transform mass spectrometry of glycosaminoglycan carbohydrates. European Journal of Mass Spectrometry 2011, 17 (2), 167-176.

6.         Sanderson, P.;  Stickney, M.;  Leach III, F. E.;  Xia, Q.;  Yu, Y.;  Zhang, F.;  Linhardt, R. J.; Amster, I. J., Heparin/heparan sulfate analysis by covalently modified reverse polarity capillary zone electrophoresis-mass spectrometry. Journal of Chromatography A 2018, 1545, 75-83.