Structure and anticoagulant activity of a fucosylated chondroitin sulfate from echinoderm. Sulfated fucose branches on the polysaccharide account for its high anticoagulant action

Paulo A.S. Mourao, Mariana S. Pereira, Mauro S.G. Pavo, Barbara Mulloy, Douglas M. Tollefsen, Marie Christine Mowinckel, Ulrich Abildgaard

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Abstract

A polysaccharide isolated from the body wall of the sea cucumber Ludwigothurea grisea has a backbone like that of mammalian chondroitin sulfate: [4-β-D-GlcA-1→-3β-D-GalNAc-1](n) but substituted at the 3- position of the β-D-glucuronic acid residues with sulfated α-L- fucopyranosyl branches (Vieira, R. P., Mulloy, B., and Mourao, P. A. S. (1991) J. Biol. Chem. 266, 13530-13536). Mild acid hydrolysis removes the sulfated α-L-fucose branches, and cleaved residues have been characterized by 1H NMR spectroscopy; the most abundant species is fucose 4-O-monosulfate, but 2,4- and 3,4-di-O-sulfated residues are also present. Degradation of the remaining polysaccharide with chondroitin ABC lyase shows that the sulfated α-L-fucose residues released by mild acid hydrolysis are concentrated toward the non-reducing end of the polysaccharide chains; enzyme-resistant polysaccharide material includes the reducing terminal and carries acid- resistant L-fucose substitution. The sulfated α-L-fucose branches confer anticoagulant activity on the polysaccharide. The specific activity of fucosylated chondroitin sulfate in the activated partial thromboplastin time assay is greater than that of a linear homopolymeric α-L-fucan with about the same level of sulfation; this activity is lost on defucosylation or desulfation but not on carboxyl-reduction of the polymer. Assays with purified reagents show that the fucosylated chondroitin sulfate can potentiate the thrombin inhibition activity of both antithrombin and heparin cofactor II.

Original languageEnglish
Pages (from-to)23973-23984
Number of pages12
JournalJournal of Biological Chemistry
Volume271
Issue number39
DOIs
StatePublished - 1996

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