Modification and Potential Uses of Heparin and Other Acidic Polysaccharides

Abstract

Heparin lo a polydisperse, highly sulfated, linear polysaccharide of repeating uronic acid and glucosamine residues (Figure 1). Although heperin has been used clinically as an anticoagulant for the past 5O years, its precise structure remains unknown [1]. Heparin is biosynthesized as a proteoglycan (PG, Mr~1 million) consisting of a central core protein from which 10-11 long, linear polysaccharide chains extend [2]. The drug heparin is recovered from porcine 1ntestinal musosa or bovine lung as a glycosaminoglycan (GAG), a linear polysaccharide chain without anyassociated protein. GAG heparin has a Mr ranging from 5,000-40,000 (degree of polymerization (dp) 10-80) with an Mr(avg) of 13,000. Even the heporln chain corresponding to the most prevalent dp represents a mere 5 mo1% of a typical GAG heparin preparation [3]. GAG heparln has a second level of structuralcomplexity associated with its primary structure or sequence [4].