Heparan sulfate - a polyanion with multiple messages

Proteoglycans are composed of sulfate-substituted, negatively charged glycosaminoglycan chains that are covalently linked to proteins. Studies on proteoglycan biosynthesis have been focused on the isolation and molecular cloning of the various enzymes that catalyze this process. Enzymes involved in the biosynthesis of heparin and heparan sulfate include the glycosyltransferases responsible for generating the initial (GlcA-GlcNAc)(n) chains, the GlcNAc N-deacetylase/N-sulfotransferase that introduces N-sulfate groups, the D-GlcA C5-epimerase that generates L-IdoA units, and O-sulfotransferases that sulfate hydroxyl groups in various positions. Restricted polymer modification will lead to the generation of complex saccharide sequences of varied structure. Attempts have been made to define the minimal saccharide sequences required for binding of various proteins of biological interest, including growth factors of the fibroblast growth factor family. It is proposed that many ''heparin-binding proteins'', with affinity for the predominant structure in the highly sulfated heparin molecule, may bind to distinct, less modified, regions of heparan sulfate chains. These studies are expected to promote our understanding of the regulatory mechanisms behind polysaccharide biosynthesis, and of the physiological roles of proteoglycans. Further, they may provide the basis for the generation of novel drugs.