Anticoagulant and antithrombotic activities of modified xylofucan sulfate from the brown alga Punctaria plantaginea. (20th January 2016)

• Record Type: Journal Article
• Authors: Ustyuzhanina, Nadezhda E.; Bilan, Maria I.; Gerbst, Alexey G.; Ushakova, Natalia A.; Tsvetkova, Eugenia A.; Dmitrenok, Andrey S.; Usov, Anatolii I.; Nifantiev, Nikolay E.
• Is Part Of: Carbohydrate polymers. Volume 136(2016)
• Page Start: 826
• Page End: 833
• Publication Date: 2016-01-20
• Subjects: Punctaria plantaginea -- Fucan sulfate -- Anticoagulant -- Antithrombotic -- Thrombin -- Docking; Polysaccharides -- Periodicals; Polysaccharides -- Periodicals; Polysaccharides -- Périodiques; Electronic journals; 547.78
• DOI: 10.1016/j.carbpol.2015.09.102
• Languages: English
• ISSNs: 0144-8617

Abstract

Highlights: Chemical modifications of sulfated xylofucan gave derivatives with regular structure. Highly sulfated linear fucans inhibit clot formation and platelets aggregation. Persulfated fucans potentiate thrombin and factor Xa inhibition by ATIII. Docking study suggested formation of a ternary complex thrombin-ATIII-fucan. Abstract: Selectively and totally sulfated (1 → 3)-linked linear homofucans bearing ∼20 monosaccharide residues on average have been prepared from the branched xylofucan sulfate isolated from the brown alga Punctaria plantaginea . Anticoagulant and antithrombotic properties of the parent biopolymer and its derivatives were assessed in vitro . Highly sulfated linear fucan derivatives were shown to inhibit clot formation in APTT assay and ristocetin induced platelets aggregation, while the partially sulfated analogs were inactive. In the experiments with purified proteins, fucan derivatives with degree of sulfation of ∼2.0 were found to enhance thrombin and factor Xa inhibition by antithrombin III. The effect of sulfated fucans on thrombin inhibition, which was similar to those of heparinoid Clexane ® (enoxaparin) and of a fucoidan from the brown alga Saccharina latissima studied previously, can be explained by the multicenter interaction and formation of a ternary complex thrombin–antithrombin III–polysaccharide. The possibility of such complexation was confirmed by computer docking study.