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Abstract:

The anticoagulant behavior of sulfated polysaccharides from seaweeds is reviewed based on their chemical structures. Analysis of the literature suggested that the driving force for the formation of the sulfated polysaccharide/ protein complex is the non-specific polar interaction between the negatively and positively charged groups in the polysaccharide and protein, respectively and that the complex is further stabilized by short-range interactions. The polysaccharide binding site should be able to go through the following conformational steps in the formation of the complex: random coil→ordered conformation→low distortion of this conformation to form a complementary fitting structure with the protein backbone. The sulfated monosaccharide units with the highest potential for anticoagulant activity should have two sulfate groups and a glycosidic linkage on the pyranose ring with C-2, C-3 and C-4 in 2S, 3R, 4R or 2R, 3S, 4S configurations for galactose, fucose and arabinose and 2S, 3S, 4R, for rhamnose. Three distributions of these substituents appear: 3-linked 2,4-disulfated units, 4-linked 2,3-disulfated units and 2-linked 3,4-disulfated residues. These types of units have the possibility, through the equilibrium of the chair conformations, to place their sulfate groups in adequate spacial positions to interact with basic groups of the protein. The anticoagulant activity is mainly attributed to thrombin inhibition mediated by antithrombin and/or heparin cofactor II, with different effectivenesses depending of the compound. Other mechanisms are also proposed and these differences could be attributed to the diversity of structures of the polysaccharides evaluated and to the fact that one compound may have more than one target protease. © 2010 Bentham Science Publishers Ltd.

Registro:

Documento: Artículo
Título:Overview of anticoagulant activity of sulfated polysaccharides from seaweeds in relation to their structures, focusing on those of green seaweeds
Autor:Ciancia, M.; Quintana, I.; Cerezo, A.S.
Filiación:Cátedra 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
CIHIDECAR-CONICET, Departamento de Química Orgánica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria, Pabellón 2, 1428 Buenos Aires, Argentina
Laboratorio de Hemostasia y Trombosis, Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria, Pabellón 2, 1428 Buenos Aires, Argentina
Palabras clave:anticoagulant activity; chemical structure; disulfated structural units; green seaweed; structure-activity relationship; Sulfated polysaccharides; antithrombin; arabinose; carbohydrate; fucose; galactose; glycosaminoglycan; heparin cofactor II; monosaccharide; polysaccharide; rhamnose; sulfate; thrombin; anticoagulant therapy; article; drug activity; drug binding; drug conformation; drug inhibition; drug mechanism; drug structure; human; hydrophobicity; nonhuman; seaweed; structure activity relation; Animals; Anticoagulants; Blood Coagulation; Humans; Molecular Structure; Polysaccharides; Seaweed; Sulfates
Año:2010
Volumen:17
Número:23
Página de inicio:2503
Página de fin:2529
DOI: http://dx.doi.org/10.2174/092986710791556069
Título revista:Current Medicinal Chemistry
Título revista abreviado:Curr. Med. Chem.
ISSN:09298673
CODEN:CMCHE
CAS:antithrombin, 9000-94-6; arabinose, 147-81-9; fucose, 3615-37-0, 3713-31-3; galactose, 26566-61-0, 50855-33-9, 59-23-4; heparin cofactor II, 81604-65-1; rhamnose, 10485-94-6, 3615-41-6; sulfate, 14808-79-8; thrombin, 869858-13-9, 9002-04-4; Anticoagulants; Polysaccharides; Sulfates
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_09298673_v17_n23_p2503_Ciancia

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Citas:

---------- APA ----------
Ciancia, M., Quintana, I. & Cerezo, A.S. (2010) . Overview of anticoagulant activity of sulfated polysaccharides from seaweeds in relation to their structures, focusing on those of green seaweeds. Current Medicinal Chemistry, 17(23), 2503-2529.
http://dx.doi.org/10.2174/092986710791556069
---------- CHICAGO ----------
Ciancia, M., Quintana, I., Cerezo, A.S. "Overview of anticoagulant activity of sulfated polysaccharides from seaweeds in relation to their structures, focusing on those of green seaweeds" . Current Medicinal Chemistry 17, no. 23 (2010) : 2503-2529.
http://dx.doi.org/10.2174/092986710791556069
---------- MLA ----------
Ciancia, M., Quintana, I., Cerezo, A.S. "Overview of anticoagulant activity of sulfated polysaccharides from seaweeds in relation to their structures, focusing on those of green seaweeds" . Current Medicinal Chemistry, vol. 17, no. 23, 2010, pp. 2503-2529.
http://dx.doi.org/10.2174/092986710791556069
---------- VANCOUVER ----------
Ciancia, M., Quintana, I., Cerezo, A.S. Overview of anticoagulant activity of sulfated polysaccharides from seaweeds in relation to their structures, focusing on those of green seaweeds. Curr. Med. Chem. 2010;17(23):2503-2529.
http://dx.doi.org/10.2174/092986710791556069