[The great Scandinavian Jahre Prize 1993. What is the function of heparan sulfate?]

The polysaccharide heparin, produced by mast cells, had been used in the prophylaxis and treatment of thrombotic disease long before the molecular mechanism responsible for its anticoagulant activity was elucidated. The anticoagulant effect is particularly dependent upon the presence of a specific pentasaccharide sequence, which binds to the proteinase inhibitor, antithrombin. Detailed knowledge of this mechanism enabled the development of low-molecular weight heparin with improved therapeutic properties. Studies on the biosynthesis of heparin have revealed the essential features of the generation of such complex saccharide sequences, the initial formation of a simple, repetitive polymer is followed by the action of a number of modifying enzymes. Though the mode of regulation of these enzymes is still only partly understood, heparan sulphate, structurally related to heparin, has been found to be generated by virtually all the mammalian cells studied, and is typically exposed as a proteoglycan at cell surfaces. Recent findings suggest specific heparan sulphate sequences to be crucially involved in the action of certain growth factors.