Glycosaminoglycans (GAGs) are the most acidic naturally occurring biopolymers, found in the extracellular matrices. These complex polysaccharides play key roles in regulating the biological activity of several proteins including those in the coagulation cascade, growth factors, cytokine, chemokines, enzymes such as lipoprotein lipases and surface proteins on virus and parasites. The relationship between structure and activity of HLGAGs is still very poorly understood due to the complexity and heterogeneity of these polymers. In this application novel methods to rapidly separate and characterize di and oligosaccharides found in HLGAGs are proposed. A quantitative analysis of the constituent oligosaccharides would enable determining compositional analysis of HLGAG fragments, analogous to AAA for proteins. Such an compositional analysis would provide valuable information not only regarding the overall chemical properties of the GAG samples but also enable comparison of different GAG fractions with interesting biological attributes. This could serve as a quality control benchmark to eliminate batch-to-batch variations observed in the commercial preparations of HLGAGs for therapeutic applications. Furthermore, generating information regarding the overall compositions of the disaccharide would be a first step towards a more challenging problem of sequencing the GAG chain in a systematic fashion.
The demand for determining oligosaccharide compositional analysis, especially for complex oligosaccharide such as heparin is very high. Novel methodologies in this direction would enable the establishment of a commercial core facility for oligosaccharide analysis and potentially sequencing of the saccharide chains.
