Journal
CURRENT PHARMACEUTICAL DESIGN
Volume 10, Issue 9, Pages 967-981Publisher
BENTHAM SCIENCE PUBL LTD
DOI: 10.2174/1381612043452730
Keywords
sulfated fucan; sulfated galactan; fucoidan; algal polysaccharides; marine invertebrates; heparin; anticoagulant activity; antithrombotic activity
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Sulfated alpha-L-fucans from brown algae (also known as fucoidan) have complex and heterogeneous structures but recent studies revealed the occurrence of ordered repeat units in the sulfated fucans from several species. Even in these cases, the presence of highly branched portions and the complex distributions of sulfate and acetyl groups highlight the heterogeneity of algal fucans. Another source of sulfated alpha-L-fucans (and their parental compounds sulfated alpha-L-galactans and fucosylated chondroitin sulfate) is marine invertebrates. The invertebrate polysaccharides have simple, ordered structures, which differ in the specific patterns of sulfation and/or position of the glycosidic linkages within their repeating units. The algal and invertebrate sulfated fucans have potent anticoagulant activity, mediated by antithrombin and/or heparin cofactor II. As most of the studies were carried out with algal fucans it was not easy to trace a structure versus activity relationship. This aspect was clarified as studies were extended to invertebrate polysaccharides. These definitively established that regular, linear sulfated alpha-L-fucans and sulfated alpha-L-galactans express anticoagulant activity, which is not simply a function of charge density, but depends critically on the pattern of sulfation and monosaccharide composition. Sulfated alpha-L-fucans and fucosylated chondroitin sulfate also express antithrombotic activity when tested on in vivo models of venous and arterial thrombosis in experimental animals. These polysaccharides constitute potential therapeutic compounds as alternative to heparin and may help to design structure-based drugs with specific activity on each type of thrombosis episode and few side effects. They can also serve as research reagents to investigate and distinguish among a variety of interrelated events, such as coagulation, bleeding, thrombosis and platelet aggregation.
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