Towards Synthesis of Heparan Sulfate Glycopeptides and Proteoglycans
Proteoglycans are an important family of glycoproteins, consisting of a core protein bearing one of more glycosaminoglycan chain(s), mainly through tetrasaccharide linkers. Both the core protein and glycan chains have been shown to play important roles in their multi-faceted biological functions. As proteoglycans are highly heterogeneous in nature due to structural variations of the glycan chains, synthesis has become a preferred approach to enable access to well-defined proteoglycans. This chapter starts with an overview of the structures, function and biosynthesis of proteoglycans. Subsequently, synthesis of the tetrasaccharide linker of proteoglycans through either chemical or enzymatic methods is discussed. This is followed by a review of synthetic efforts towards producing heparan sulfate proteoglycans. Currently, glycopeptides bearing multiple glycan chains including sulfated heparan sulfate oligosaccharides can be synthesized. Challenges in stereochemical control during glycosylation, protective group chemistry, integrating glycan with peptide chemistry, and the low reactivity and specificity of currently available enzymes are discussed to spur further developments in synthesis of this class of important biomolecules.