Synthesis of heparan sulfate glycosaminoglycan (HS GAG) libraries for unlocking the sulfation code and understanding GAG biology

Abstract

The complex sulfation patterns of heparan sulfate glycosaminoglycans (HS GAGs) are crit. for many important biol. processes such as viral invasion, growth factor signaling, blood coagulation and cancer. However, an understanding of their specific functions has been hampered by an inability to synthesize comprehensive libraries of HS oligosaccharides representing all of the diverse sulfation motifs. We will describe new methods to accelerate the synthesis of HS GAGs and enable generation of large collections of HS oligosaccharides. These mols. are invaluable for unlocking the "sulfation code" and understanding the roles of specific sulfation motifs in human physiol. and disease. Toward this end, we will also discuss the application of defined HS mols. and chem. tools to the discovery of a novel interaction between HS GAGs and an orphan receptor, Tie1. These studies provide insights into the mechanisms by which HS regulates cellular signaling pathways and plays a key role in the maturation and remodeling of the vasculature.