title: Anticoagulant and antithrombotic activities of modified xylofucan sulfate from the brown alga Punctaria plantaginea.
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.
authors.affiliation: N.D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Leninsky Prospect 47, B-334, 119991 Moscow, Russian Federation.
authors.forename: Nadezhda E
authors.initials: NE
authors.lastname: Ustyuzhanina
authors.affiliation: N.D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Leninsky Prospect 47, B-334, 119991 Moscow, Russian Federation.
authors.forename: Maria I
authors.initials: MI
authors.lastname: Bilan
authors.affiliation: N.D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Leninsky Prospect 47, B-334, 119991 Moscow, Russian Federation.
authors.forename: Alexey G
authors.initials: AG
authors.lastname: Gerbst
authors.affiliation: V.N. Orekhovich Institute of Biomedical Chemistry, Russian Academy of Medical Sciences, Pogodinskaya Str. 10, 119121 Moscow, Russian Federation.
authors.forename: Natalia A
authors.initials: NA
authors.lastname: Ushakova
authors.affiliation: N.D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Leninsky Prospect 47, B-334, 119991 Moscow, Russian Federation.
authors.forename: Eugenia A
authors.initials: EA
authors.lastname: Tsvetkova
authors.affiliation: N.D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Leninsky Prospect 47, B-334, 119991 Moscow, Russian Federation.
authors.forename: Andrey S
authors.initials: AS
authors.lastname: Dmitrenok
authors.affiliation: N.D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Leninsky Prospect 47, B-334, 119991 Moscow, Russian Federation.
authors.forename: Anatolii I
authors.initials: AI
authors.lastname: Usov
authors.affiliation: N.D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Leninsky Prospect 47, B-334, 119991 Moscow, Russian Federation. Electronic address: nen@ioc.ac.ru.
authors.forename: Nikolay E
authors.initials: NE
authors.lastname: Nifantiev
mesh_terms: D000595:Amino Acid Sequence; D000925:Anticoagulants / Q000737:chemistry* / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects; D006801:Humans; D008969:Molecular Sequence Data; D000459:Phaeophyceae / Q000737:chemistry; D010936:Plant Extracts / Q000737:chemistry* / Q000494:pharmacology; D010975:Platelet Aggregation Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D011134:Polysaccharides / Q000737:chemistry* / Q000494:pharmacology; D011485:Protein Binding; D013917:Thrombin / Q000737:chemistry / Q000378:metabolism; D014994:Xylose / Q000031:analogs & derivatives* / Q000737:chemistry
chemical_list: D000925:Anticoagulants; D010936:Plant Extracts; D010975:Platelet Aggregation Inhibitors; D011134:Polysaccharides; C007789:fucoidan; D014994:Xylose; D013917:Thrombin
keywords: Anticoagulant; Antithrombotic; Docking; Fucan sulfate; Punctaria plantaginea; Thrombin