title: Selective sulfation of carrageenans and the influence of sulfate regiochemistry on anticoagulant properties.
abstract: Sulfated polysaccharides are recognized for their broad range of biological activities, including anticoagulant properties. The positions occupied by the sulfate groups are often related to the level of the inherent biological activity. Herein the naturally sulfated galactans, kappa-, iota- and theta-carrageenan, were additionally sulfated by regioselective means. The anticoagulant activity of the resulting samples was then studied using the aPTT in vitro assay. The influence of sulfate regiochemistry on the anticoagulant activity was evaluated. From kappa-carrageenan three rare polysaccharides were synthesized, one of them involved a synthetic route with an amphiphilic polysaccharide intermediate containing pivaloyl groups. Iota- and theta-carrageenan were utilized in a selective C6 sulfation at β-D-Galp units to produce different structures comprising trisulfated diads. All the samples were characterized by NMR (1D and 2D). The resulting aPPT measurements suggested that sulfation at C2 of 3,6-anhydro-α-D-Galp and C6 of β-D-Galp increased the anticoagulant activity.
authors.affiliation: Departamento de Bioquímica e Biologia Molecular, Universidade Federal do Paraná, Centro Politécnico CEP 81-531-990, PO Box 19046, Curitiba, Brazil.
authors.forename: Cristiano A
authors.initials: CA
authors.lastname: de Araújo
authors.forename: Miguel D
authors.initials: MD
authors.lastname: Noseda
authors.forename: Thales R
authors.initials: TR
authors.lastname: Cipriani
authors.forename: Alan G
authors.initials: AG
authors.lastname: Gonçalves
authors.forename: Maria Eugênia R
authors.initials: ME
authors.lastname: Duarte
authors.forename: Diogo R B
authors.initials: DR
authors.lastname: Ducatti
mesh_terms: D000925:Anticoagulants / Q000737:chemistry / Q000494:pharmacology*; D002351:Carrageenan / Q000737:chemistry* / Q000302:isolation & purification; D005685:Galactans / Q000737:chemistry; D006801:Humans; D019906:Nuclear Magnetic Resonance, Biomolecular; D010314:Partial Thromboplastin Time; D013329:Structure-Activity Relationship; D013431:Sulfates
chemical_list: D000925:Anticoagulants; D005685:Galactans; D013431:Sulfates; D002351:Carrageenan