Dissection of heparin-past and future

When compared to other complex carbohydrate polymers. heparin and heparan sulfate present unique challenges for structural characterization. Special finesse must be used to determine their monoor disaccharide compositions, their sulfate contents, and their disaccharide sequences Approaches that have been developed for addressing these difficult problems include selective enzyme cleavage, selective nitrous acid cleavage with or without N-deacetylation of the GlcNAc's, reduction of the GlcA and IdoA residues to labilize their glycosidic bonds, periodate oxidation to allow selective cleavage at the unsulfated uronic acid residues, and ion exchange and reversed phase ion pairing HPLC to resolve complex mixtures of di-, tetraand hexasaccharides. These techniques have been useful in determining the structure-activity relationships for the anticoagulant activity of heparin. However, heparin and heparan sulfate have many additional biological activities, and, for the most part, the specific sequences responsible for these activities are unknown. In the fbture, the isolation of specific heparin sequences will yield only small amounts of specific heparin sequences. The application of the structural methodologies described to these future changes is