Glycomics profiling of heparan sulfate structure and activity

Abstract

The heparan sulfate (HS) family of glycosaminoglycans are highly complex and structurally diverse polysaccharides with information encoded within the chains that imparts the ability to bind selectively to a wide range of proteins-the "HS interactome"-and to regulate their biological activities. However, there are two key questions which need to be addressed; first, the extent of structural variation of expressed HS structures-the "heparanome"-in specific biological contexts and second, the degree of functional selectivity exerted by these structures in regulating biological processes. There is a clear need to develop more systematic and high throughput approaches in order to address these questions. Here, we describe a cohort of protocols for profiling different aspects of HS structure and activity, focusing particularly on disaccharide building blocks and larger oligosaccharide domains, the latter representing the functional units of HS chains. A range of other complementary methods in the literature are also discussed. Together these provide a new and more comprehensive toolkit to investigate HS structure and activity in a higher throughput manner in selected biological systems. The implementation of such a glycomics strategy will enable development of a systems biology view of HS structure-function relationships and help to resolve the significant puzzle of the extensive interactome of HS, which remains a key question in the glycobiology field. We anticipate that the next decade will see major advances in our understanding of the complex biology of HS.