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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.


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
Página de inicio:2503
Página de fin:2529
Título revista:Current Medicinal Chemistry
Título revista abreviado:Curr. Med. Chem.
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


  • Kelton, J.G., Warkentin, T.E., Heparin-induced thrombocytopenia: A historical perspective (2008) Blood, 112, pp. 2607-2616
  • Kelton, J.G., Hirsh, J., Bleeding associated with antithrombotic therapy (1980) Semin. Hematol., 17, pp. 259-291
  • Anand, S., Yusuf, S., Pogue, J., Ginsberg, J., Hirsh, J., Relationship of Activated Partial Thromboplastin Time to Coronary Events and Bleeding in Patients with Acute Coronary Syndromes who Receive Heparin (2003) Circulation, 107, pp. 2884-2888
  • Duarte, M.E.R., Cardoso, M.A., Noseda, M.D., Cerezo, A.S., Structural studies on fucoidans from the brown seaweed Sargassum stenophyllum (2001) Carbohydr. Res., 333, pp. 281-293
  • Stortz, C.A., Cerezo, A.S., Novel findings in carrageenans, agarans and "hybrid" red seaweed galactans (2000) Curr. Topics Phytochem., 4, pp. 121-134
  • Yermak, I.M., Khotimchenko, Y.S., Chemical properties, biological activities and applications of carrageenans from red seaweeds. In Recent Advances in Marine Biotechnology (2003) Biomaterils and Bioprocessing, 9, pp. 207-255. , ed. Fingerman, M.; Nagabhushanam, R., Science Publishers, Inc
  • Damonte, E.B., Matulewicz, M.C., Cerezo, A.S., Sulfated seaweed polysaccharides as antiviral agents (2004) Curr. Med. Chem., 18, pp. 2399-2419
  • Schaeffer, D.J., Krylov, V.S., Anti-HIV activity of extracts and compounds from algae and cyanobacteria (2000) Ecotoxicol. Environ. Saf., 45, pp. 208-227
  • Pujol, C.A., Carlucci, M.J., Matulewicz, M.C., Damonte, E.B., Natural sulfated polysaccharides for the prevention and control of viral infections (2007) Top Heterocycl. Chem., 11, pp. 259-281
  • Ghosh, T., Chattopadhyay K.;Marschall, M., Karmakar, P., Mandal, P., Ray, B., Focus on antivirally active sulfated polysaccharides: From structure-activity analysisto clinical evaluation (2009) Glycobiol., 19, pp. 2-15
  • McLellan, D.S., Jurd, K.M., Anticoagulants from marine algae (1992) Blood Coag. Fibrinil, 3, pp. 69-77
  • Matsubara, K., Recent advances in marine algal anticoagulants (2004) Curr Med. Chem. - Cardiovasc. Hematol. Agents, 2, pp. 13-19
  • Soeda, S., Kozako, T., Iwata, K., Shimeno, H., Oversulfated fucoidan inhibits the basic fibroblast growth factor-induced tube formation by human umbilical vein endothelial cells: Its possible mechanism of action (2000) Bichim. Biophys. Acta, 1497, pp. 127-134
  • Matsubara, K., Mori, M., Matsumoto, H., Hori, K., Mayazawa, K., Antiangioginic properties of a sulfatedf galactan isolated from a marine green alga, Codium cylindricum (2003) J. Appl. Phycol., 15, pp. 87-90
  • Nika, K., Mulloy, B., Carpenter, B., Gibbs, R., Specific recognition of immunecytokines by sulphated polysaccharides from marine algae (2003) Eur. J. Phycol., 38, pp. 257-264
  • Schepetkin, I.A., Quinn, M.T., Botanical polysaccharides: Macrophage immunomodulation and therapeutic potential (2006) Int. Immunopharmacol., 6, pp. 317-333
  • Goff, L.J., Liddle, L., Silva, P.C., Voytek, M., Coleman, A.W., Tracing species invasion in Codium, a siphonous green seaweed, using molecular tools (1992) Am. J. Bot., 79, pp. 1279-1285
  • Stam, T.W., Meusnier, I., Destombe, C., Valero, M., Olsen, J.L., Tracing invasions of Caulerpa taxifolia with molecular markers (2002) J. Phycol., 38, pp. 33-34
  • Hoffman, M., Monroe, D.M., A cell-based model of hemostasis (2001) Thromb. Haemost., 85, pp. 958-965
  • Teien, A.N., Abildgaard, U., Höök, M., The anticoagulant effect of heparan sulfate and dermatan sulfate (1976) Thromb. Res., 8, pp. 859-867
  • Olson, S.T., Björk, I., Regulation of thrombin activity by antithrombin and heparin (1994) Semin. Thromb. Hemost., 20, pp. 373-409
  • Thunberg, L., Bäckström, G., Lindahl, U., Further characterization of the antithrombin-binding sequence in heparin (1982) Carbohydr Res., 100, pp. 393-410
  • Olson, S.T., Björk, I., Sheffer, R., Craig, P.A., Shore, J.D., Choay, J., Role of the antithrombin-binding pentasaccharide in heparin acceleration of antithrombin-proteinase reactions. Resolution of the antithrombin conformational change contribution to heparin rate enhancement (1992) J. Biol. Chem., 267, pp. 12528-12538
  • Hoylaerts, M., Owen, W.G., Collen, D., Involvement of heparin chain length in the heparin-catalyzed inhibition of thrombin by antithrombin III (1984) J. Biol. Chem., 259, pp. 5670-5677
  • Danielsson, A., Raub, E., Lindahl, U., Björk, I., Role of ternary complexes, in which heparin binds both antithrombin and proteinase, in the acceleration of the reactions between antithrombin and thrombin or factor Xa (1986) J. Biol. Chem., 261, pp. 15467-15473
  • Olson, S.T., Halvorson, H.R., Björk, I., Quantitative characterization of the thrombin-heparin interaction. Discrimination between specific and nonspecific binding models (1991) J. Biol. Chem., 266, pp. 6342-6352
  • Ferro, D.R., Provasoli, A., Ragazzi, M., Casu, B., Torri, G., Bossennec, V., Perly, B., Choay, J., Conformer populations of L-iduronic acid residues in glycosaminoglycan sequences (1990) Carbohydr. Res., 195, pp. 157-167
  • Mulloy, B., Forster, M.J., Jones, C., Davies, D.B., N.m.r. and molecular- modelling studies of the solution conformation of heparin (1993) Biochem. J., 293, pp. 849-858
  • Tollefsen, D.M., Pestka, C.A., Monafo, W.J., Activation of heparin cofactor II by dermatan sulfate (1983) J. Biol. Chem., 258, pp. 6713-6716
  • Maimone, M.M., Tollefsen, D.M., Structure of a dermatan sulfate hexasaccharide that binds to heparin cofactor II with high affinity (1990) J. Biol. Chem., 265, pp. 18263-18271
  • Mascellani, G., Liverani, L., Prete, A., Bergonzini, G.L., Bianchini, P., Silvestro, L., Torri, G., Casu, B., Active sites of dermatan sulfate frp heparin cofactor II. Isolation of a nonasaccharide fragment containing four disaccharide sequences [α-L-iduronic acid 2-O-sulfate (1,3)-β-D-N-acetylgalactosamine 4-sulfate] (1995) J. Carbohydr. Chem., 14, pp. 1165-1177
  • Tollefsen, D.M., Insight into the mechanism of action of heparin cofactor II (1995) Thromb Haemost., 74, pp. 1209-1214
  • Verhamme, I.M., Bock, P.E., Jackson, C.M., The preferred pathway of glycosaminoglycan-accelerated inactivation of thrombin by heparin cofactor II (2004) J. Biol. Chem., 279, pp. 5785-5795
  • Chaidedgumjorn, A., Toyoda, H., Woo, E.R., Lee, K.B., Kim, Y.S., Toida, T., Imanari, T., Effect of (1→3)- and (1→4)-linkages of fully sulfated polysaccharides on their anticoagulant activity (2002) Carbohydr. Res., 337, pp. 925-933
  • Jozefowicz, M., Jozefowicz, J., Randomness and biospecificity: Random copolymers are capable of biospecific molecular recognition in living systems (1997) Biomaterial, 18, pp. 1633-1644
  • Rees, D.A., (1977) Polysaccharide Shapes, , Chapman and Hall: London
  • Katchalsky, A., Polyelectrolites and their biological interactions (1964) Biophys. J., 4, pp. 9-41
  • Wall, D., Douglas, S., Ferro, V., Cowden, W., Parish, C., Characterisation of the anticoagulant properties of a range of structurally diverse sulfated oligosaccharides (2001) Thromb. Res., 103, pp. 325-335
  • Volpi, N., Characterization of heparins with different relative molecular masses (from 11600 to 1600) by various analytical techniques (1993) J. Chrom., 622, pp. 13-20
  • Guerrini, M., Guglieri, S., Naggi, A., Sasisekharan, R., Torri, G., Low molecular weight heparins: Structural differentiation by bidimensional nuclear magnetic resonance spectroscopy (2007) Semin. Thromb. Hemost., 33, pp. 478-487
  • Katsuraya, K., Ikushima, N., Takahashi, N., Shoji, T., Nakashima, H., Yamamoto, N., Yoshida, T., Urdu, T., Synthesis of sulfated alkyl malto- and laminara-oligosaccharides with potent inhibitory effects on AIDS virus infection (1994) Carbohydr. Res., 260, pp. 51-61
  • Huynh, R., Chaubet, F., Jozefonvicz, J., Anticoagulant properties of dextranmethylcarboxylate benzylamide sulfate (DMCBSu); a new generation of bioactive functionalized dextran (2001) Carbohydr. Res., 332, pp. 75-83
  • Huang, R., Du, Y., Yang, J., Fan, L., Influence of functional groups on the in vitro anticoagulant activity of chitosan sulfate (2003) Carbohydr. Res., 338, pp. 483-489
  • Tyler-Cross, R., Harris, R.B., Sobel, M., Marques, D., Heparin binding domain peptides of antithrombin III: Analysis by isothermal titration calorimetry and circular dichroism spectroscopy (1994) Prot. Sci., 3, pp. 620-627
  • Raman, R., Venkataraman, G., Ernst, S., Sasiseklaran, V., Sasiseklaran, R., Structural specificity of heparin binding in the fibroblast growth factor family of protein (2003) Proc. Natl. Acad. Sci. USA, 100, pp. 2357-2363
  • Kolender, A.A., Matulewicz, M.C., Cerezo, A.S., Structural analysis of antiviral sulfated α-D-(1→3)-linked mannans (1995) Carbohydr. Res., 273, pp. 179-185
  • Feldman, S.C., Reynaldi, S., Stortz, C.A., Cerezo, A.S., Damonte, E.B., Antiviral properties of fucoidan fractions from Leathesia difformis (1999) Phytomed., 6, pp. 335-340
  • Matulewicz, M.C., Cerezo, A.S., The carrageenan from Iridaea undulosa B.; Analysis, Fractionation and alkaline treatment (1980) J. Sci. Food Agric., 31, pp. 203-213
  • Nardella, A., Chaubet, F., Boisson-Vidal, C., Blondin, C., Durand, P., Jozefonvicz, J., Anticoagulant low molecular weight fucans produced by radical process and ion exchange chromatography of high molecular weight fucans extracted from the brown seaweed Ascophyllum nodosum (1996) Carbohydr. Res., 289, pp. 201-208
  • Nishino, T., Nagumo, T., The sulfate-content dependence of the anticoagulant activity of a fucan sulfate from the brown seaweed Ecklonia kurome (1991) Carbohydr. Res., 214, pp. 193-197
  • Nishino, T., Nagumo, T., Anticoagulant and antithrombin activities of oversulfated fucans (1992) Carbohydr. Res., 229, pp. 355-362
  • Pavão, M.S.G., Aiello, K.R.M., Werneck, C.C., Silva, L.C.F., Valente, A.P., Mulloy, B., Colwelli, N.S., Mourão, P.A.S., Highly Sulfated Dermatan Sulfates from Ascidians. Structure versus anticoagulant activity of these glycosamineglycans (1998) J. Biol. Chem., 273, pp. 27848-27857
  • Carlucci, M.J., Pujol, C.A., Ciancia, M., Noseda, M.D., Matulewicz, M.C., Damonte, E.B., Cerezo, A.S., Antiherpetic and anticoagulant properties of carrageenans from the red seaweed Gigartina skottsbergii and their cyclized derivatives: Correlation between structure and biological activity (1997) Int. J. Biol. Macromol., 20, pp. 97-105
  • Jurd, K.M., Rogers, D.J., Blunden, G., McLellan, D.S., Anticoagulant properties of sulphated polysaccharides and a proteoglycan from Codium fragile ssp. atlanticum (1995) J. Appl. Phycol., 7, pp. 339-345
  • Siddhanta, A.K., Shanmugam, M., Mody, K.H., Goswami, A.M., Ramabat, B.K., Sulphated polysaccharides of Codium dwarkense Boergs. from the west coast of India: Chemical composition and blood anticoagulant activity (1999) Int. J. Biol. Macromol., 26, pp. 151-154
  • Alban, S., Franz, G., Partial synthetic glucan sulfates as potential new antithrombotics: A review (2001) Biomacromolecule, 2, pp. 354-361
  • Yang, J., Du, Y., Huang, R., Wan, Y., Wen, Y., The structureanticoagulant activity relationships of sulfated lacquer polysaccharide. Effect of carboxyl group and position of sulfation (2005) Int. J. Biol. Macromol., 36, pp. 9-15
  • Nishimura, S.-I., Nishi, N., Tokura, S., Okiei, W., Somorin, O., Inhibition of the hydrolytic activity of thrombin by chitin heparinoids (1986) Carbohydr. Res., 156, pp. 286-292
  • Maaroufi, R.M., Jozefowicz, M., Tapon-Bretaudiere, J., Fischer, A.M., Thrombin inhibition by antithrombin in the presence of oversulfated dermatan sulfates (2006) Carbohydr. Res., 341, pp. 672-676
  • Bourin, M.C., Lundgren-Akerlund, E., Lindahl, U., Isolation and characterization of the glycosaminoglycan component of rabbit thrombomodulin proteoglycan (1990) J. Biol. Chem., 265, pp. 15424-15431
  • Maruyama, T., Toida, T., Imanari, T., Yu, G., Linhardt, R.J., Conformational changes and anticoagulant activity of chondroitin sulfate following its O-sulfonation (1998) Carbohydr. Res., 306, pp. 35-43
  • Aspinall, G.O., (1983) The polysaccharides, 2, pp. 1-9. , In, G.O. Aspinall, Ed.; Academic Press: New York-London
  • Pereira, M.S., Melo, F.R., Mourão, P.A.S., Is there a correlation between structure and anticoagulant action of sulfated galactans and sulfated fucans? (2002) Glycobiology, 12, pp. 573-580
  • Pomin, V.H., Mourão, P.A.S., Structure, biology, evolution, and medical importance of sulfated fucans and galactans (2008) Glycobiology, 18, pp. 1016-1027
  • Ciancia, M., Noseda, M.D., Matulewicz, M.C., Cerezo, A.S., Alkali-modification of carrageenans: Mechanism and kinetics in the kappa/iota-, mu/nu- and lambda-series (1993) Carbohydr. Pol., 20, pp. 95-98
  • Morris, E.R., Rees, D.A., Welsh, E.J., Dunfield, L.G., Whittington, S.G., Relation between primary structure and chain flexibility of random coil polysaccharides: Calculation and experiment for a range of model carrageenans (1978) J. Chem. Soc. Perkin II, pp. 793-800
  • Kindness, G., Long, W.F., Williamson, F.B., Anticoagulant effect of sulphated polysaccharides in normal antithhrombin III-deficient plasmas (1980) Br. J. Pharmacol., 69, pp. 675-677
  • Güven, L.C., Özsoy, Y., Ulutin, O.N., Anticoagulant, fibrinolytic and antiaggregant activity of carrageenans and alginic acid (1991) Bot. Mar., 34, pp. 429-432
  • Farias, W.R.L., Valente, A.P., Pereira, M.S., Mourão, P.A.S., Structure and anticoagulant activity of sulfated galactans. Isolation of a unique sulfated galactan from the red algae Bothyocladia occidentalis and comparison of its anticoagulant action with that of sulfated galactans from invertebrates (2000) J. Biol. Chem., 275, pp. 29299-29307
  • Pereira, M.G., Benevides, N.M.B., Melo, M.R.S., Valente, A.P., Melo, F.R., Mourão, P.A.S., Structure and anticoagulant activity of a sulfated galactan from the red alga, Gelidium crinale. Is there a specific structural requirement for the anticoagulant action? (2005) Carbohydr. Res., 340, pp. 2015-2023
  • Blunden, G., Rogers, D.J., Carpenter, B.C., McLellan, D.S., Smith, B.E., Carabot Cuervo, A., Morales Mendez, A., Rosquete, C., Lectinas, agents antihemostáticos y compuestos positivos al reactivo de Dragendorff en algas marinas de Venezuela y Túnez (1991) Rev. Fac. Farm. Venezuela (Mérida), 28, pp. 25-28
  • Duarte, M.E.R., Cauduro, J.P., Noseda, D.G., Noseda, M.D., Gonçalves, A.G., Pujol, C.A., Damonte, E.B., Cerezo, A.S., The structure of the agaran sulfate from Acanthophora spicifera (Rhodomelaceae, Ceramiales) and its antiviral activity. Relation between structure and antiviral activity in agarans (2004) Carbohydr. Res., 339, pp. 335-347
  • Hawkins, W.W., Leonard, V.G., Antipeptic and antithrombic properties of carrageenin (1962) J. Lab. Clin. Med., 60, pp. 641-648
  • Hawkins, W.W., Leonard, V.G., The antithrombic activity of carrageenin in human blood (1963) Can. J. Biochem. Physiol., 41, pp. 1325-1327
  • Farias, W.R.L., Nasareth, R.A., Mourao, P.A.S., Dual effect of sulfated galactans from the red seaweed Botriocladia occidentalis preventingthrombosis and inducing platelet aggregation (2001) Thromb. Haemost., 86, pp. 1540-1546
  • Melo, F.R., Pereira, M.S., Monteiro, R.Q., Foguel, D., Mourão, P.A.S., Sulfated galactan is a catalyst of antithrombin-mediated inactivation of alpha-thrombin (2008) Biochim. Biophys. Acta, 1780 (9), pp. 1047-1053
  • Fonseca, R.J., Oliveira, S.N., Melo, F.R., Pereira, M.G., Benevides, N.M., Mourão, P.A.S., Slight differences in sulfation of algal galactans account for differences in their anticoagulant and venous antithrombotic (2008) Thromb. Haemost., 99, pp. 539-545
  • Nishino, T., Kiyohara, H., Yamada, H., Nagumo, T., An anticoagulant fucoidan from the brown seaweed Ecklonia kurome (1991) Phytochem., 30, pp. 535-539
  • Nagaoka, M., Shibata, H., Kimura-Takagi, I., Hashimoto, S., Kimura, K., Makino, T., Aiyama, R., Yokokura, T., Structural study of fucoidan from Cladosiphon okamuranus tokida (1999) Glycoconj. J., 16, pp. 19-26
  • Usov, A.I., Smirnova, G.P., Bilan, M.I., Shashkov, A.S., Polysaccharides of Algae: 53. Brown Alga Laminaria saccharina(L.) Lam. as a source of Fucoidan (1998) Russ. J. Bioorg. Chem., 24, pp. 382-389
  • Chizhov, A.O., Dell, A., Morris, H.R., Haslam, S.M., McDowell, R.A., Shashkov, A.S., Nifantev, N.E., Usov, A.I., A study of fucoidan from the brown seaweed Chorda filum (1999) Carbohydr. Res., 320, pp. 108-119
  • Chevolot, L., Foucault, A., Chaubet, F., Kervarec, N., Sinquin, C., Fisher, A.M., Boisson-Vidal, C., Further data on the structure of brown seaweed fucans: Relationships with anticoagulant activity (1999) Carbohydr. Res., 319, pp. 154-165
  • Chevolot, L., Mulloy, B., Ratiskol, J., Foucault, A., Colliec-Jouault, S., A disaccharide repeat unit is the major structure in fucoidans from two species of brown algae (2001) Carbohydr. Res., 330, pp. 529-535
  • Marais, M.F., Joseleau, J.-P., A fucoidan fraction from Ascophyllum nodosum (2001) Carbohydr. Res., 336, pp. 155-159
  • Nishino, T., Nishioka, C., Ura, H., Nagumo, T., Isolation and partial characterization of a noval amino sugar-containing fucan sulfate from commercial Fucus vesiculosus fucoidan (1994) Carbohydr. Res., 255, pp. 213-224
  • Bilan, M.I., Grachev, A.A., Ustuzhanina, N.E., Shashkov, A.S., Nifantiev, N.E., Usov, A.I., Structure of a fucoidan from the brown seaweed Fucus evanescens C.Ag (2002) Carbohydr. Res., 337, pp. 719-730
  • Cumashi, A., Ushakova, N.A., Preobrazhenskaya, M.E., D'Incecco, A., Piccoli, A., Totani, L., Tinari, N., Nifantiev, N.E., A comparative study of the antiinflammatory, anticoagulant, antiangiogenic, and antiadhesive activities of nine different fucoidans from brown seaweeds (2007) Glycobiol., 17, pp. 541-552
  • Sakai, T., Shimanaka, K., Ikai, K., Kato, I., Structures of oligosaccharides derived from Cladosiphon okamuranus fucoidan by digestion with marine bacterial enzymes (2003) Mar. Technol., 5, pp. 536-544
  • Carvalho, G., de Azevedo, T., Bezerra, M.E.B., Santos, M.G.L., Souza, L.A., Marques, C.T., Benevides, N.M.B., Lisboa Leite, E., Heparinoids algal and their anticoagulant, hemorrhagic activities and platelet aggregation Biomed. Pharmacother, , in press. [Epub ahead of print]
  • Nishino, T., Takabe, Y., Nagumo, T., Isolation and partial characterization of a novel β-d-galactan sulfate from the brown seaweed Laminaria angustata var. longissima (1994) Carbohydr. Pol., 23, pp. 165-173
  • Nishino, T., Nagumo, T., Kiyohara, H., Yamada, H., Structural characterization of a new anticoagulant fucan sulfate from the brown seaweed Ecklonia kurome (1991) Carbohydr. Res., 211, pp. 77-90
  • Mourão, P.A.S., Pereira, M.S., Pavão, M.S.G., Mulloy, B., Tollefsen, D.M., Mowinckel, M.-C., Abildgaard, U., Structure and anticoagulant activity of a Fucosylated Chondroitin sulfate from Echinoderm. Sulfated fucose branches on the polysaccharide account for its high anticoagulant action (1996) J. Biol. Chem., 271, pp. 23976-23984
  • van Boeckel, C.A.A., Petitou, M., The Unique Antithrombin III Binding Domain of Heparin: A Lead to New Synthetic Antithrombotics (1993) Angew. Chem. Int. Ed. Engl., 32, pp. 1671-1690
  • Church, F.C., Meade, J.B., Treanor, R.E., Whinna, H.C., Antithrombin activity of fucoidan. The interaction of fucoidan with heparin cofactor II, antithrombin III, and thrombin (1989) J. Biol. Chem, 264, pp. 3618-3623
  • Nishino, T., Aizu, Y., Nagumo, T., Antithrombin activity of a fucan sulfate from the brown seaweed Ecklonia kurome (1991) Thromb. Res., 62, pp. 765-773
  • Nishino, T., Aizu, Y., Nagumo, T., The influence of sulfate content and molecular weight of a fucan sulfate from the brown seaweed Ecklonia kurome on its antithrombin activity (1991) Thromb. Res., 64, pp. 723-731
  • Mauray, S., Sternberg, C., Theveniaux, J., Millet, J., Sinquin, C., Tapon-Bretaudière, J., Fischer, A.M., Venous antithrombotic and anticoagulant activities of a fucoïdan fraction (1995) Thromb. Haemost., 74, pp. 1280-1285
  • Nishino, T., Fukuda, A., Nagumo, T., Fujihara, M., Kaji, E., Inhibition of the generation of thrombin and factor Xa by a fucoidan from the brown seaweed Ecklonia kurome (1999) Thromb. Res., 96, pp. 37-49
  • Pereira, M.S., Mulloy, B., Mourão, P.A., Structure and anticoagulant activity of sulfated fucans. Comparison between the regular, repetitive, and linear fucans from echinoderms with the more heterogeneous and branched polymers from brown algae (1999) J. Biol. Chem., 274, pp. 7656-7667
  • Yoon, S.J., Pyun, Y.R., Hwang, J.K., Mourão, P.A., A sulfated fucan from the brown alga Laminaria cichorioides has mainly heparin cofactor II-dependent anticoagulant activity (2007) Carbohydr. Res., 342, pp. 2326-2330
  • Lahaye, M., Robic, A., Structure and functional properties of Ulvan, a polysaccharide from green seaweeds (2007) Biomacromol., 8, pp. 1766-1774
  • Mao, W., Zang, X., Li, Y., Zhang, H., Sulfated polysaccharides from marine green algae Ulva conglobata and their anticoagulant activity (2006) J. Appl. Phycol., 18, pp. 9-14
  • Athukorala, Y., Lee, K.-W., Kim, S.-K., Jeon, Y.-J., Anticoagulant activity of marine green and brown algae collected from Jeju Island in Korea (2007) Biores. Technol., 98, pp. 1711-1716
  • Maeda, M., Uehara, T., Harada, N., Sekiguchi, M., Hiraoka, A., Heparinoid-active sulphated polysaccharides from Monostroma nitidum and their distribution in the chlorophyta (1991) Phytochemistry, 30, pp. 3611-3614
  • Hayakawa, Y., Hayashi, T., Lee, J.-B., Srisomporn, P., Maeda, M., Ozawa, T., Sakuragawa, N., Inhibition of thrombin by sulfated polysaccharides isolated from green seaweeds (2000) Biochim. Biophys. Acta, 1543, pp. 86-94
  • Mao, W.J., Fang, F., Li, H.Y., Qi, X.H., Sun, H.H., Chen, Y., Guo, S.D., Heparinoid-active two sulfated polysaccharides isolated from marine green algae Monostroma nitidum (2008) Carbohyd. Polym., 74, pp. 834-839
  • Mao, W., Li, H., Li, Y., Zhang, H., Qi, X., Sun, H., Chen, Y., Guo, S., Chemical characteristic and anticoagulant activity of the sulfated polysaccharide isolated from Monostroma latissimum (Chlorophyta) (2009) Int. J. Biol. Macromol., 44, pp. 70-74
  • Zhang, H.J., Mao, H.J., Fang, F., Li, H.Y., Sun, H.H., Chen, Y., Qi, X.H., Chemical characteristics and anticoagulant activities of a sulfated polysaccharide and its fragments from Monostroma latissimum (2008) Carbohydr. Pol., 71, pp. 428-434
  • Cassolato, J.E.F., Noseda, M.D., Pujol, C.A., Pellizzari, F.M., Damonte, E.B., Duarte, M.A.R., Chemical structure and antiviral activity of the sulfated heterorhamnan isolated from the green seaweed Gayralia oxysperma (2008) Carbohydr. Res., 343, pp. 3085-3095
  • Harada, N., Maeda, M., Chemical structure of antithrombin-active Rhamnan sulfate from Monostroma nitidum (1998) Biosci. Biotechnol. Biochem., 62, pp. 1647-1652
  • Ciancia, M., Quintana, I., Vizcargüénaga, M.I., Kasulin, L., de Dios, A., Estevez, J.M., Cerezo, A.S., Polysaccharides from the green seaweeds Codium fragile and C. vermilara with controversial effects on hemostasis (2007) Int. J. Biol. Macromol., 41, pp. 641-649
  • Estevez, J.M., Fernández, P.V., Kasulin, L., Dupree, P., Ciancia, M., Chemical and in situ characterization of macromolecular components of the cell walls from the green seaweed Codium fragile (2009) Glycobiol., 19, pp. 212-228
  • Deacon-Smith, R.A., Lee-Potter, J.P., Rogers, D.A., Anticoagulant activity in extracts of British marine algae (1985) Bot. Mar., 28, pp. 333-338
  • Blunden, G., Rogers, D.J., Carpenter, B.C., McLellan, D.S., Smith, B.E., Carabot, C.A., Morales, M.A., Rosquete, C., Lectinas, agents antihemostáticos y compuestos positivos al reactivo de Dragendorff en algas marinas de Venezuela y Túnez (1991) Rev. Fac. Farm. Venezuela (Mérida), 28, pp. 25-28
  • Rogers, D.A., Jurd, K.M., Blunden, G., Paoletti, S., Zanetti, F., Anticoagulant activity of a proteoglycan in extracts from Codium fragile ssp. atlanticum (1990) J. Appl. Phycol., 2, pp. 357-361
  • Uehara, T., Takeshita, M., Maeda, M., Studies on anticoagulantactive arabinan sulfates from the green alga, Codium latum (1992) Carbohydr. Res., 23, pp. 309-311
  • Matsubara, K., Matsuura, Y., Hori, K., Miyazawa, K., An anticoagulant proteoglycan from the marine green alga, Codium pugniformis (2000) J. Appl. Phycol., 12, pp. 9-14
  • Matsubara, K., Matsuura, Y., Bacic, A., Liao, M.L., Hori, K., Miyazawa, K., Anticoagulant properties of a sulfated galactan preparation from a marine green alga, Codium cylindricum (2001) Int. J. Biol. Macromol., 28, pp. 395-399
  • Backinowsky, L.V., Nepogod'ev, S.A., Kochetkov, N.K., Stereospecific synthesis of a (1→5)-α-L-arabinan (1985) Carbohydr. Res., 137, pp. C1-C3
  • Watanabe, T., Inaba, K., Nakai, A., Mitsunaga, T., Ohnishi, J., Koshijima, T., Water-soluble polysaccharides from the root of Pinus densiflora (1991) Phytochemistry, 30, pp. 1425-1429
  • Love, J., Percival, E., The polysaccharides of the green seaweed Codium fragile : Part II. The water-soluble sulphated polysaccharides (1964) J. Chem. Soc., pp. 3338-3345
  • Nika, K., Mulloy, B., Carpenter, B., Gibbs, R., Specific recognition of immunecytokines by sulphated polysaccharides from marine algae (2003) Eur. J. Phycol., 38, pp. 257-264
  • Bilan, M.I., Vinogradova, E.V., Shashkov, A.S., Usov, A.I., Isolation and preliminary characterization of a highly pyruvylated galactan from Codium yezoense (Bryopsidales, Chlorophyta) (2006) Bot Mar., 49, pp. 259-262
  • Bilan, M.I., Vinogradova, E.V., Shashkov, A.S., Usov, A.I., Structure of a highly pyruvylated galactan sulfate from the pacific green alga Codium yezoense (Bryopsidales, Chlorophyta) (2007) Carbohydr. Res., 342, pp. 586-596
  • Farias, E.H.C., Pomin, V.H., Valente, A.P., Nader, H.B., Rocha, H.A.O., Mourão, P.A.S., A preponderantly 4-sulfated, 3-linked galactan from the green alga Codium isthmocladum (2008) Glycobiol., 18, pp. 250-259
  • Ohta, Y., Lee, J.B., Hayashi, K., Hayashi, T., Isolation of Sulfated Galactan from Codium fragile and Its Antiviral Effect, (2009) Biol. Pharmacol. Bull., 32, pp. 892-898
  • Binkley, R.W., (1988) Modern Carbohydrate Chemistry Marcel Dekker Inc., , in, NY-Basel
  • Margalit, M., Fischer, N., Ben-Sasson, S.A., Comparative analysis of structurally defined heparin binding sequences reveals a distinct spatial distribution of basic residues (1993) J. Biol. Chem., 268, pp. 19228-19231
  • Soler Ferran, D., Sobel, M., Harris, R.B., Design and synthesis of a helix heparin-binding peptide (1992) Biochemistry, 31, pp. 5010-5016
  • Sobel, M., Soler, D.F., Kermode, J.C., Harris, R.B., Localization and characterization of a heparin binding domain peptide of human von Willebrand factor (1992) J. Biol. Chem., 267, pp. 8857-8862
  • Tyler Cross, R., Sobel, M., Marques, D., Soler, D.F., Harris, R.B., Heparin-von willebrand factor binding as assessed by isothermal titration calorimetry and by affinity fractionation of heparins using synthetic peptides (1993) Arch. Biopchem. Biophys., 306, pp. 528-533
  • Mulloy, B., Mourão, P.A.S., Gray, E., Structure/function studies of anticoagulant sulphated polysaccharides using NMR (2000) J. Biotechnol., 77, pp. 123-135
  • Margalit, H., Fischer, N., Ben-Sasson, S.A., Comparative analysis of structurally defined heparin binding sequences reveals a distinct spatial distribution of basic residues (1993) J. Biol. Chem., 268, pp. 19228-19231
  • Maccarana, M., Casu, B., Lindahl, U., Minimal sequence in heparin/ heparin sulfate required for binding of basic fibroblast growth factor (1993) J. Biol. Chem., 268, pp. 23898-905


---------- 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.
---------- 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.
---------- 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.
---------- 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.