Importance of the Fine Structure of Glycolsaminoglycans

The identification of distinct saccharide sequences that have specific functions, such as a sulfated pentasaccharide sequence in heparin for antithrombin III-binding, is rare. Based on structural studies of sulfated glycosaminoglycans, a set of oligosaccharide sequences with different sulfation patterns, or “wobble motifs,” recognized by a single protein were found. However, there are still questions about the structure–function relationships of sulfated glycosaminoglycans. The glucosamine 3-O-sulfate structure, which is a minor component (less than 10%) in heparan sulfate/heparin, is especially of interest. Although glucosamine 3-O-sulfate is a rare structure, heparan sulfate 3-O-sulfotransferase is the most varied among heparan sulfate sulfotransferases. Therefore, other saccharide sequences including a 3-O-sulfated glucosamine residue may be needed for binding to proteins similar to the sequence for antithrombin-III-binding. Oligosaccharides isolated from naturally occurring polysaccharides after depolymerization have been used for the analysis of their biological activities to elucidate structure–function relationships. However, only the major sequences in the polysaccharide were tested under this oligosaccharide preparation method. Relatively minor and unique structures may influence the selectivity and interaction of glycosaminoglycans with functional proteins. Chemoenzymatic methods have used as an effective approach for the synthesis of variously sulfated oligosaccharides of glycosaminoglycans. These synthetic oligosaccharide libraries will become a major resource for the functional analysis of sulfated glycosaminoglycans.