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Abstract
Glycosaminoglycans (GAGs) are long linear polysaccharides with a repeating uronic acid sugar and amino sugar disaccharide backbone that can be heavily modified. These modifications make GAGs highly negatively charged and contribute to GAGs being a major player in many important biological processes. Intact GAGs are typically too long and complex to analyze with mass spectrometry (MS) and completely digested GAG disaccharides provide valuable statistical data but are too short to retain binding motifs. Partially digested GAG chains are the best way to characterize structural modifications that make up binding motifs, but partial digestion often presents samples that are highly complex and full of isomers. Online separation paired with MS is the best way to simplify complex biological GAG samples for tandem MS analysis. Capillary zone electrophoresis separations are designed for highly charged samples like GAGs and separate samples based on their charge to size ratio. Negative electron transfer dissociation is a fast electron-based ion activation technique that works well within online separation time limitations and enables fragmentation and characterization of GAGs without loss of informative sulfo-modifications. A CZE-MS platform and method optimized for GAG separations and analysis would be a powerful tool for biological research that could enhance our understanding of disease and biological operations.