Glycosaminoglycans (GAGs) are an important class of carbohydrates that play a central role in a number of biological processes, and their structural analysis is a target of substantial research effort. Taken as a whole, glycosaminoglycans (GAGs) represent a challenging class of molecules to analyze due to their heterogeneity, the lability of sulfation modifications and the difficulty of distinguishing subtle structural differences, such as uronic acid stereochemistry. The last few years has seen considerable progress in GAG analysis by mass spectrometry with the introduction of supercharging methods for stabilizing sites of sulfation, chemical modification methods to replace sulfates with more stable functional groups, and novel methods of ion activation, such as electron detachment dissociation (EDD). We have investigated the applicability of EDD for fully characterizing several classes of GAGs with a single stage of tandem mass spectrometry. EDD has shown great utility for analyzing oligosaccharides from chondroitin/dermatan sulfate, heparan sulfate, and heparin. Generally speaking, EDD provides more structural detail than more widely used ion activation methods such as collision induced dissociation (CID) or infrared multiphoton photodissociation (IRMPD), and is less likely to lead to sulfate decomposition. Highly sulfated heparins have remained the most challenging of all GAG oligosaccharides to analyze. Surprisingly, we have recently found that CID is useful for this challenging class of GAGs if all of the ionizable protons are replaced by sodium ions. The evolution of tandem mass spectrometry approaches for GAG analysis, and the recent discovery of a tandem mass spectrometry approach for characterizing highly-sulfated GAGs will be presented.

Advances in the mass spectrometry analysis of heparinoids and other highly sulfated glycosaminoglycans

245th National Meeting (2013)

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