A highly sulfated pyranosic (1?_3)-?Ò-L-arabinan with anticoagulante activity. Mechanism of action

CIANCIA, MARINA; PAULA VIRGINIA FERNÁNDEZ; IRENE QUINTANA; ALBERTO S. CEREZO; JOSE ESTEVEZ

Sorrento

Simposio; 16th European Carbohydrate Symposium; 2011

Universidad de Napoles

A highly sulfated pyranosic (1®3)-β-L-arabinan with anticoagulant activity. MECHANISM OF ACTION Marina Ciancia1,2, Paula Virginia Fernández1, Irene Quintana3, Alberto Saúl Cerezo2, José Manuel Estevez4 1Cátedra de Química de Biomoléculas, Departamento de Biología Aplicada y Alimentos, Facultad de Agronomía, Universidad de Buenos Aires, Av. San Martín 4453, 1417 Buenos Aires, Argentina.2CIHIDECAR-CONICET, Departamento de Química Orgánica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria, Pabellón 2, 1428 Buenos Aires, Argentina. 3Laboratorio de Hemostasia y Trombosis, Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria - Pabellón 2, C1428EHA Buenos Aires, Argentina. 4Departamento de Fisiología, Biología Molecular y Celular (IFIByNE-CONICET), Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria - Pabellón 2, 1428 Buenos Aires, Argentina. E-mail: ciancia@agro.uba.ar The room temperature water extract obtained from green seaweed Codium vermilara1 was fractionated by addition of KCl to give solutions of increasing concentrations of this salt. Only one insoluble product was obtained at 0.115 M (Ab) in 31% yield, which contained 97% of L-arabinose, a sulfate/arabinose molar ratio of 1.8/1, an [α]D = + 167.5 º, and a number average molecular weight of 180 KDa. Methylation analysis of Ab and its desulfated derivative (DAb) showed that this polysaccharide is mainly constituted by 3-linked 2,4-disulfated arabinopyranosyl residues, although some mono- and non-sulfated units are also present. Analysis of the corresponding NMR spectra confirmed this structure and showed that these units are in the β?configuration. This product showed a high anticoagulant activity, but lower than that of heparin, as 5 and 0.65 mg/ml, respectively were necessary to increase the clotting time in APTT assay in 2.5 times. The coagulation mechanism is in part through the direct inhibition of thrombin, although inhibition of thrombin by potentiation of antithrombin and heparin cofactor II was also found by amydolitic methods. In conclusion, a highly sulfated pyranosic β-l-arabinan was isolated from the cell walls of a green seaweed. It showed anticoagulant behaviour by a mechanism different to that of heparin. To the best of our knowledge, this is the first report in nature of a polysaccharide constituted only by arabinose residues in the pyranosic form. Reference 1.        Marina Ciancia, Irene Quintana, María I. Vizcargüénaga, Luciana Kasulin,  Agustina de Dios, José Manuel Estevez, Alberto S. Cerezo, Int. J. Biol. Macromol., 2007, 41, 641-649.