Structural characterization, in vitro anticoagulant, and antiplatelet activities of a Distolasterias nipon dermatan sulfate-like polymer with a distinctive sulfation pattern.

A novel dermatan sulfate-like polysaccharide (DNP) was isolated from the body walls of the starfish Distolasterias nipon. Its structure was elucidated using chemical methods and 2D NMR spectroscopy, revealing a backbone of →4)-α-L-IdopA-(1→3)-β-D-GalpNAc-(1→, with the α-L-iduronic acid residues predominantly 2,3-di-O-sulfated, alongside 2-O- and 3-O-monosulfated variants, and the β-D-GalpNAc residues 4-O-sulfated. Functional assays showed that DNP prolongs thrombin time (TT) comparable to heparin and more potently than enoxaparin (Clexane®), whereas its effect on activated partial thromboplastin time (APTT) is less pronounced. The anticoagulant activity of DNP is characterized by antithrombin-dependent thrombin inhibition and moderate suppression of factor Xa. Furthermore, the polysaccharide does not induce platelet aggregation nor interfere with physiological ADP-mediated pathways, but it inhibits ristocetin-induced aggregation. These findings identify D. nipon as a source of a dermatan sulfate structurally distinct from those found in other starfishes and invertebrates, and characterized by an antithrombin-dependent anti-IIa/anti-Xa profile and additional antiplatelet properties.