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Is there a correlation between structure and anticoagulant action of sulfated galactans and sulfated fucans?
Glycobiology. 2002 Oct; 12(10):573-80.G

Abstract

We attempted to identify the specific structural features in sulfated galactans and sulfated fucans that confer anticoagulant activity. For this study we employed a variety of invertebrate polysaccharides with simple structures composed of well-defined units of oligosaccharides. Our results indicate that a 2-O-sulfated, 3-linked alpha-L-galactan, but not a alpha-L-fucan with a similar molecular size, 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 replaced thrombin. The occurrence of 2,4-di-O-sulfated units is an amplifying motif for 3-linked alpha-fucan-enhanced thrombin inhibition by antithrombin. If we replace antithrombin by heparin cofactor II, then the major structural requirement for the activity becomes single 4-O-sulfated fucose units. The presence of 2-O-sulfated fucose residues always had a deleterious effect on anticoagulant activity. Overall, our results indicate that the structural requirements for interaction of sulfated galactans and sulfated fucans with coagulation cofactors and their target proteases are stereospecific and not merely a consequence of their charge density and sulfate content.

Authors+Show Affiliations

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.No affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

12244069

Citation

Pereira, Mariana S., et al. "Is There a Correlation Between Structure and Anticoagulant Action of Sulfated Galactans and Sulfated Fucans?" Glycobiology, vol. 12, no. 10, 2002, pp. 573-80.
Pereira MS, Melo FR, Mourão PA. Is there a correlation between structure and anticoagulant action of sulfated galactans and sulfated fucans? Glycobiology. 2002;12(10):573-80.
Pereira, M. S., Melo, F. R., & Mourão, P. A. (2002). Is there a correlation between structure and anticoagulant action of sulfated galactans and sulfated fucans? Glycobiology, 12(10), 573-80.
Pereira MS, Melo FR, Mourão PA. Is There a Correlation Between Structure and Anticoagulant Action of Sulfated Galactans and Sulfated Fucans. Glycobiology. 2002;12(10):573-80. PubMed PMID: 12244069.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Is there a correlation between structure and anticoagulant action of sulfated galactans and sulfated fucans? AU - Pereira,Mariana S, AU - Melo,Fábio R, AU - Mourão,Paulo A S, PY - 2002/9/24/pubmed PY - 2003/4/19/medline PY - 2002/9/24/entrez SP - 573 EP - 80 JF - Glycobiology JO - Glycobiology VL - 12 IS - 10 N2 - We attempted to identify the specific structural features in sulfated galactans and sulfated fucans that confer anticoagulant activity. For this study we employed a variety of invertebrate polysaccharides with simple structures composed of well-defined units of oligosaccharides. Our results indicate that a 2-O-sulfated, 3-linked alpha-L-galactan, but not a alpha-L-fucan with a similar molecular size, 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 replaced thrombin. The occurrence of 2,4-di-O-sulfated units is an amplifying motif for 3-linked alpha-fucan-enhanced thrombin inhibition by antithrombin. If we replace antithrombin by heparin cofactor II, then the major structural requirement for the activity becomes single 4-O-sulfated fucose units. The presence of 2-O-sulfated fucose residues always had a deleterious effect on anticoagulant activity. Overall, our results indicate that the structural requirements for interaction of sulfated galactans and sulfated fucans with coagulation cofactors and their target proteases are stereospecific and not merely a consequence of their charge density and sulfate content. SN - 0959-6658 UR - https://www.unboundmedicine.com/medline/citation/12244069/Is_there_a_correlation_between_structure_and_anticoagulant_action_of_sulfated_galactans_and_sulfated_fucans DB - PRIME DP - Unbound Medicine ER -