GLYCOSAMINOGLYCANS - SYNTHETIC FRAGMENTS AND THEIR INTERACTION WITH SERINE-PROTEASE INHIBITORS

Glycosaminoglycans such as e.g, heparin, heparan sulphate and dermatan sulphate display a broad variety of biological activities. Unique, we ll-defined domains in some glycosaminoglycans have been characterized that are responsible for the biological activity. For instance, a uniq ue pentasaccharide domain in heparin could be identified which binds a nd activates the serine protease inhibitor (serpin) anti-thrombin III (AT III). The structure-activity relationships of various synthetic co unter-parts of the heparin pentasaccharide fragment reveal the highly specific nature of the pentasaccharide mediated activation of AT III. With the aid of molecular modelling and the availability of crystal st ructures of serpins and their target proteases, the activation process of AT III by heparin becomes understood at the molecular level. Some attention will also be paid to well-defined domains in heparan sulphat e and dermatan sulphate.