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A 2-sulfated, 3-linked alpha-L-galactan is an anticoagulant polysaccharide.
Carbohydr Res. 2002 Nov 19; 337(21-23):2231-8.CR

Abstract

Marine alga is an abundant source of sulfated polysaccharides with potent anticoagulant activity. However, several attempts to identify the specific structural features in these compounds, which confer the biological activity, failed due to their complex, heterogeneous structure. We isolated and characterized several sulfated alpha-L-galactans and sulfated alpha-L-fucans from marine invertebrates. In contrast to the algal fucans and galactans, these invertebrate polysaccharides have a simple structure, composed of well-defined units of oligosaccharides. We employed two of these compounds to elucidate their structure-anticoagulant action relationship. Our results indicate that a 2-sulfated, 3-linked alpha-L-galactan, but not an alpha-L-fucan, is a potent thrombin inhibitor mediated by antithrombin or heparin cofactor II. The difference between the activities of these two polysaccharides is not very pronounced when factor Xa replaces thrombin. Thus, the anticoagulant activity of sulfated galactan and sulfated fucan is not merely a consequence of their charge density. The interaction of these polysaccharides with coagulation cofactors and their target proteases are specific. Identification of specific structural requirements in sulfated galactans and sulfated fucans necessary for interaction with coagulation cofactors is an essential step for a more rational approach to develop new anticoagulant and antithrombotic drugs.

Authors+Show Affiliations

Pereira MS
Laboratório de Tecido Conjuntivo, Hospital Universitário Clementino Fraga Filho and Departamento de Bioquímica Médica, Centro de Ciências da Saúde, Universidade Federal do Rio de Janeiro, Caixa Postal 68041, Rio de Janeiro RJ 21941-590, Brazil.
Vilela-Silva AC
No affiliation info available
Valente AP
No affiliation info available
Mourão PA
No affiliation info available

MeSH

AnimalsAnticoagulantsAntithrombin IIIBlood Coagulation TestsDrug InteractionsFactor Xa InhibitorsGalactansHeparin Cofactor IIHumansPolysaccharidesSea UrchinsStructure-Activity RelationshipSulfuric Acid EstersThrombin

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

12433487

Citation

Pereira, Mariana S., et al. "A 2-sulfated, 3-linked alpha-L-galactan Is an Anticoagulant Polysaccharide." Carbohydrate Research, vol. 337, no. 21-23, 2002, pp. 2231-8.
Pereira MS, Vilela-Silva AC, Valente AP, et al. A 2-sulfated, 3-linked alpha-L-galactan is an anticoagulant polysaccharide. Carbohydr Res. 2002;337(21-23):2231-8.
Pereira, M. S., Vilela-Silva, A. C., Valente, A. P., & Mourão, P. A. (2002). A 2-sulfated, 3-linked alpha-L-galactan is an anticoagulant polysaccharide. Carbohydrate Research, 337(21-23), 2231-8.
Pereira MS, et al. A 2-sulfated, 3-linked alpha-L-galactan Is an Anticoagulant Polysaccharide. Carbohydr Res. 2002 Nov 19;337(21-23):2231-8. PubMed PMID: 12433487.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A 2-sulfated, 3-linked alpha-L-galactan is an anticoagulant polysaccharide. AU - Pereira,Mariana S, AU - Vilela-Silva,Ana-Cristina E S, AU - Valente,Ana-Paula, AU - Mourão,Paulo A S, PY - 2002/11/16/pubmed PY - 2003/7/12/medline PY - 2002/11/16/entrez SP - 2231 EP - 8 JF - Carbohydrate research JO - Carbohydr Res VL - 337 IS - 21-23 N2 - Marine alga is an abundant source of sulfated polysaccharides with potent anticoagulant activity. However, several attempts to identify the specific structural features in these compounds, which confer the biological activity, failed due to their complex, heterogeneous structure. We isolated and characterized several sulfated alpha-L-galactans and sulfated alpha-L-fucans from marine invertebrates. In contrast to the algal fucans and galactans, these invertebrate polysaccharides have a simple structure, composed of well-defined units of oligosaccharides. We employed two of these compounds to elucidate their structure-anticoagulant action relationship. Our results indicate that a 2-sulfated, 3-linked alpha-L-galactan, but not an alpha-L-fucan, is a potent thrombin inhibitor mediated by antithrombin or heparin cofactor II. The difference between the activities of these two polysaccharides is not very pronounced when factor Xa replaces thrombin. Thus, the anticoagulant activity of sulfated galactan and sulfated fucan is not merely a consequence of their charge density. The interaction of these polysaccharides with coagulation cofactors and their target proteases are specific. Identification of specific structural requirements in sulfated galactans and sulfated fucans necessary for interaction with coagulation cofactors is an essential step for a more rational approach to develop new anticoagulant and antithrombotic drugs. SN - 0008-6215 UR - https://www.unboundmedicine.com/medline/citation/12433487/A_2_sulfated_3_linked_alpha_L_galactan_is_an_anticoagulant_polysaccharide_ DB - PRIME DP - Unbound Medicine ER -
Grapherence [↓17]

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