Chemical synthesis of oligosaccharides based on heparin and heparan sulfate

Abstract

Heparin and heparan sulfate (HS) are complex polysaccharides that mediate and modulate the activity of numerous proteins. These proteins associate with the sugar's repeating disaccharide backbone, which is decorated with diverse sulfation patterns. Knowledge of the molecular details of these interactions may allow the development of new forms of diagnostic and therapeutic agents. Chemical syntheses of heparin- and HS-based oligosaccharides are vital in accessing the well-defined materials required by structure-activity relationship evaluations. These synthetic efforts, however, are confronted with several challenges such as access to the rare L-idose/L-iduronic acid derivatives, αstereoselectivity in glucosaminylation, the manner of chain elongation, the selection and manipulation of protecting groups including the introduction of sulfonate groups at defined positions, and the efficient generation of compounds that are diverse enough to represent the natural heparin and HS chains. This review focuses on our achievements in addressing these concerns together with concise descriptions of the collective solutions that have been developed thus far. We also briefly highlight the results of biological assays involving our sugar constructs. © 2013 FCCA (Forum: Carbohydrates Coming of Age).