Chemical Sulfonation and Anticoagulant Activity of Acharan Sulfate

Abstract

Acharan sulfate is a glycosaminoglycan prepared from the giant African snail, Achatina fulica. This polysaccharide has a repeating disaccharide structure of →4)-2-deoxy-2-acetamido-α-D-glucopyranose (1→4)-2-sulfo-α-L-idopyranosyluronic acid (1→). Its structure is related to heparin and heparan sulfate but is distinctly different from all known members of these classes of glycosaminoglycans. Because of its structural similarities to heparin, chemically modified acharan sulfate was studied to understand the chemical structure effected its anticoagulant activity. After de- N-acetylation, acharan sulfate was N-sulfonated using either chlorosulfonic acid-pyridine or sulfur trioxide-trimethylamine complex. The sulfate level in these products ranged from 22 to 24%(w/w), significantly less than that of heparin at 36%. The molecular weight of both N-sulfoacharan sulfates were comparable with that of heparin. In vitro anticoagulant activity assays showed that N-sulfoacharan sulfate derivatives were moderately active for the inhibition of thrombin and neither product showed any measurable anti–factor Xa activity. The differences in the activities of N-sulfoacharan sulfates produced by these two methods are probably ascribable to a small level of concomitant O-sulfonation obtained when using chlorosulfonic acid-pyridine.