Abstract
The brown alga Spatoglossum schroederi contains three fractions of sulfated polysaccharides. One of them was purified by acetone fractionation, ion exchange, and molecular sieving chromatography. It has a molecular size of 21.5 kDa and contains fucose, xylose, galactose, and sulfate in a molar ratio of 1.0:0.5:2.0:2.0 and contains trace amounts of glucuronic acid. Chemical analyses, methylation studies, and NMR spectroscopy showed that the polysaccharide has a unique structure, composed of a central core formed mainly by 4-linked beta-galactose units, partially sulfated at the 3-O position. Approximately 25% of these units contain branches of oligosaccharides (mostly tetrasaccharides) composed of 3-sulfated, 4-linked alpha-fucose and one or two nonsulfated, 4-linked beta-xylose units at the reducing and nonreducing end, respectively. This sulfated galactofucan showed no anticoagulant activity on several "in vitro" assays. Nevertheless, it had a potent antithrombotic activity on an animal model of experimental venous thrombosis. This effect is time-dependent, reaching the maximum 8 h after its administration compared with the more transient action of heparin. The effect was not observed with the desulfated molecule. Furthermore, the sulfated galactofucan was 2-fold more potent than heparin in stimulating the synthesis of an antithrombotic heparan sulfate by endothelial cells. Again, this action was also abolished by desulfation of the polysaccharide. Because this sulfated galactofucan has no anticoagulant activity but strongly stimulates the synthesis of heparan sulfate by endothelial cells, we suggested that this last effect may be related to the "in vivo" antithrombotic activity of this polysaccharide. In this case the highly sulfated heparan sulfate produced by the endothelial cells is in fact the antithrombotic agent. Our results suggested that this sulfated galactofucan may have a potential application as an antithrombotic drug.
Highlights
The leading causes of death in the United States are diseases that involve heart and blood vessels and, thrombosis
The sulfated galactofucan was 2-fold more potent than heparin in stimulating the synthesis of an antithrombotic heparan sulfate by endothelial cells. This action was abolished by desulfation of the polysaccharide. Because this sulfated galactofucan has no anticoagulant activity but strongly stimulates the synthesis of heparan sulfate by endothelial cells, we suggested that this last effect may be related to the “in vivo” antithrombotic activity of this polysaccharide
Chemical composition of acidic polysaccharides from S. schroederi obtained by acetone precipitation The chemical composition of the sulfated galactofucan fraction is indicated by italic type
Summary
The leading causes of death in the United States are diseases that involve heart and blood vessels and, thrombosis. Unfractionated heparins and low molecular weight heparins are the only sulfated polysaccharides currently used as anticoagulant drugs These compounds have several side effects such as bleeding and thrombocytopenia [2, 3]. Marine brown algae are an abundant source of anticoagulant polysaccharides They contain a variety of sulfated L-fucans with anticoagulant activity (4 –11). Each new sulfated polysaccharide purified from a marine alga is a new compound with unique structures and, with potential novel biological activities. We report the purification, structural characterization, and pharmacological activities of a new sulfated polysaccharide from the brown alga Spatoglossum schroederi. This polysaccharide has a unique structure, composed of a central core of 4-linked, partially 3-sulfated -galactose units. We attributed the antithrombotic activity of this sulfated polysaccharide to its potent effect stimulating the synthesis of a
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