Inactivation of thrombin by a fucosylated chondroitin sulfate from echinoderm

A polysaccharide extracted from the sea cucumber body wall has the same bac kbone structure as the mammalian chondroitin sulfate, but some of the glucu ronic acid residues display sulfated fucose branches. These branches confer high anticoagulant activity to the polysaccharide. Since the sea cucumber chondroitin sulfate has analogy in structure with mammalian glycosaminoglyc ans and sulfated fucans from brown algae, we compared its anticoagulant act ion with that of heparin and of a homopolymeric sulfated fucan with approxi mately the same level of sulfation as the sulfated fucose branches found in the sea cucumber polysaccharide. These various compounds differ not only i n their anticoagulant potencies but also in the mechanisms of thrombin inhi bition. Fucosylated chondroitin sulfate, like heparin, requires antithrombi n or heparin cofactor II for thrombin inhibition. Sulfated fucans from brow n algae have an antithrombin effect mediated by antithrombin and heparin co factor Il, plus a direct antithrombin effect more pronounced for some fract ions. But even in the case of these two polysaccharides, we observed some d ifferences. In contrast with heparin, total inhibition of thrombin in the p resence of antithrombin is not achieved with fucosylated chondroitin sulfat e, possibly reflecting a less specific interaction. Fucosylated chondroitin sulfate is able to inhibit thrombin generation after stimulation by both c ontact-activated and thromboplastin-activated systems. It delayed only the contact-induced thrombin generation, as expected for an anticoagulant witho ut direct thrombin inhibition. Overall, the specific spatial array of the s ulfated fucose branches in the fucosylated chondroitin sulfate not only con fer high anticoagulant activity to the polysaccharide but also determine di fferences in the way it inhibits thrombin. (C) 2001 Elsevier Science Ltd. A ll rights reserved.