Glycosaminoglycans (GAGs) are long, unbranched polysaccharides composed of repeating disaccharide units. GAGs are primarily found on the surface of cells or in the extracellular matrix[1]. They have been reported to be involved in several biological processes including abnormal expression in several diseases. There is considerable interest in elucidating how the structures of GAGs relate to their biological activity. However, the nonuniform glycan chains with varying degrees of acetylation and sulfation make GAGs particularly challenging to analyse. One approach is to perform enzymatic digestion to break down glycosaminoglycans (GAGs) into their disaccharide units, allowing for more precise analysis and characterization.
GAG disaccharides are predominantly analysed using mass spectrometry (MS) or liquid chromatography. Matrix-Assisted Laser Desorption Ionization (MALDI) of GAG disaccharide are also gaining popularity, due to their application in MALDI mass spectrometry imaging (MSI). However, due to the highly anionic nature of MALDI and the lability of sulfate modifications, the ionization efficiency is typically poor, with neutral losses observed during laser desorption ionisation. In this study, we analysed several matrices including 9-Aminoacridine (9-AA), super-2,5-dihydroxybenzoic acid (Super-DHB), ionic liquid matrix 1-methylimidazole-α-Cyano-4-hydroxycinnamic acid (CHCA) and triethylamine-α-CHCA (TEA-CHCA), to test the applicability in the ionisation and detection of various kinds of GAG disaccharides. Comparisons and evaluations were made based on ion intensity, background interference and stability of the sulfate groups. This preliminary work would lead to the identification of a suitable matrix that could be used in MALD MSI experiments to image biological tissues at high resolution.
1. Varki, A., Cummings, R. D., Esko, J. D., Freeze, H. H., Stanley, P., Bertozzi, C. R., Hart, G. W., and Etzler, M. E. (2009) Essentials of Glycobiology. Cold Spring Harbor Press, Cold Spring Harbor, NY