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 biotherapeutics3, 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.
1. Varki, A.; Cummings, R. D.; Esko, J. D.; Stanley, P.; Hart, G. W.; Aebi, M.; Darvill, A. G.; Kinoshita, T.; Packer, N. H.; Prestegard, J. H., Essentials of Glycobiology 2015.
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.