Glycosaminoglycans: Synthetic fragments and their interaction with serine protease inhibitors

Abstract

Glycosaminoglycans such as e.g. heparin, heparan sulphate and dermatan sulphate display a broad variety of biological activities. Unique, well-defined domains in some glycosaminoglycans have been characterized that are responsible for the biological activity. For instance, a unique pentasaccharide domain in heparin could be identified which binds and activates the serine protease inhibitor (serpin) anti-thrombin III (AT III). The structure-activity relationships of various synthetic counter-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 structures 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 sulphate and dermatan sulphate. © 1995 IUPAC