Analysis of the Structure of Heparin and Heparan Sulfate by High-Resolution Separation of Oligosaccharides

Abstract

Heparin and heparan sulfate are mixtures of highly sulfated linear polysaccharides having a molecular weight (MW) ranging from 5000 to 40,000 with an MW avg of 10,000 to 25,000 (1). They are members of a family of molecules called glycosaminoglycans (GAGs). Both heparin and heparan sulfate are biosynthesized as a repeating →4)α-D-GlcNpAc(1→4)-β-D-GlcAp(1→ disaccharide sequence that undergoes partial N-deacetylation followed by N-sulfation of the newly exposed amino groups, partial C-5 epimerization of D-GlcAp to L-IdoAp and O-sulfation. A single disaccharide sequence, [→4)α-D-GlcNpS6S-(1→4)-a-L-IdoAp2S (1→], accounts for 80 to 90% of the heparin polymer. Minor sequences contain (β-D-GlcAp residues, reduced sulfation as well as N-acetylation. Heparan sulfate is structurally similar to heparin but has substantially lower sulfation. Heparan sulfate consists primarily of unsulfated disaccharide [→4)α-D-GlcNpS-(1→4)-β-D-GlcAp(1 →] and monosulfated disaccharides [→4)α-D-GlcNpS-(1→4)-β-D-GlcAp(1→] and [→4)α-D-GlcNpAc6S(1→4)-β-D-GlcAp(1 →].