Recent advances in the synthesis of extensive libraries of heparan sulfate oligosaccharides for structure–activity relationship studies.

Heparan sulfate (HS) is a linear, sulfated and highly negatively-charged polysaccharide that plays important roles in many biological events. As a member of the glycosaminoglycan (GAG) family, HS is commonly found on mammalian cell surfaces and within the extracellular matrix. The structural complexities of natural HS polysaccharides have hampered the comprehension of their biological functions and structure–activity relationships (SARs). Although the sulfation patterns and backbone structures of HS can be major determinants of their biological activities, obtaining significant amounts of pure HS from natural sources for comprehensive SAR studies is challenging. Chemical and enzyme-based synthesis can aid in the production of structurally well-defined HS oligosaccharides. In this review, we discuss recent innovations enabling the syntheses of large libraries of HS and how these libraries can provide insights into the structural preferences of various HS binding proteins. [Display omitted] • Heparan sulfate plays important roles in many biological events. • The activities of heparan sulfate can be critically dependent on its fine structure. • Comprehensive libraries of heparan sulfate tetrasaccharides have been assembled. • Structure activity relationship studies can be greatly aided by the large libraries. [ABSTRACT FROM AUTHOR]