Structure and anticoagulant activity of sulfated fucans - Comparison between the regular, repetitive, and linear fucans from echinoderms with the more heterogeneous and branched polymers from brown algae

Sulfated fucans are among the most widely studied of all the sulfated polys accharides of non-mammalian origin that exhibit biological activities in ma mmalian systems. Examples of these polysaccharides extracted from echinoder ms have simple structures, composed of oligosaccharide repeating units with in which the residues differ by specific patterns of sulfation among differ ent species. In contrast the algal fucans may have some regular repeating s tructure but are clearly more heterogeneous when compared with the echinode rm fucans. The structures of the sulfated fucans from brown algae also vary from species to species. We compared the anticoagulant activity of the reg ular and repetitive fucans from echinoderms with that of the more heterogen eous fucans from three species of brown algae. Our results indicate that di fferent structural features determine not only the anticoagulant potency of the sulfated fucans but also the mechanism by which they exert this activi ty. Thus, the branched fucans from brown algae are direct inhibitors of thr ombin, whereas the linear fucans from echinoderms require the presence of a ntithrombin or heparin cofactor II for inhibition of thrombin, as reported for mammalian glycosaminoglycans, The linear sulfated fucans from echinoder ms have an anticoagulant action resembling that of mammalian dermatan sulfa te and a modest action through antithrombin. A single difference of one sul fate ester per tetrasaccharide repeating unit modifies the anticoagulant ac tivity of the polysaccharide markedly. Possibly the spatial arrangements of sulfate esters in the repeating tetrasaccharide unit of the echinoderm fuc an mimics the site in dermatan sulfate with high affinity for heparin cofac tor II.