Relation Between the Anticoagulant Activity of 1 3Glucan Sulfates and Their Cross Reaction with HITAssociated Antibodies

To establish the structural requirements for the anticoagulant activity of sulfated carbohydrates, as well as for the development of platelet-activating immune complexes in the presence of HIT antibodies, we synthesized structurally well-defined sulfated polysaccharides (Greinacher et al., 1995). The resulting (-1,3-glucan sulfates (GluS) varied in their DS, MW, sulfation pattern, and chemically introduced glycosidic side chains (Fig. 4). Although these compounds differ structurally from heparin, they exhibit structure-dependent anticoagulant as well as antithrombotic activities (Alban et al., 1995; Franz and Alban, 1995). They also induce platelet activation in the presence of HIT antibodies (Greinacher et al., 1995). Therefore, neither uronic acids, amino groups, nor the a-1,4- or (-1, 4-glycosidic linkages found in heparin are essential for these biological properties.

R** = SO3- or H or glycosidic side chain

R** = SO3- or H or glycosidic side chain

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