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Structure and anticoagulant activity of a sulfated galactan from the red alga, Gelidium crinale. Is there a specific structural requirement for the anticoagulant action?
Carbohydr Res. 2005 Sep 05; 340(12):2015-23.CR

Abstract

Marine red algae are an abundant source of sulfated galactans with potent anticoagulant activity. However, the specific structural motifs that confer biological activity remain to be elucidated. We have now isolated and purified a sulfated galactan from the marine red alga, Gellidium crinale. The structure of this polysaccharide was determined using NMR spectroscopy. It is composed of the repeating structure -4-alpha-Galp-(1-->3)-beta-Galp1--> but with a variable sulfation pattern. Clearly 15% of the total alpha-units are 2,3-di-sulfated and another 55% are 2-sulfated. No evidence for the occurrence of 3,6-anhydro alpha-galactose units was observed in the NMR spectra. We also compared the anticoagulant activity of this sulfated galactan with a polysaccharide from the species, Botryocladia occidentalis, with a similar saccharide chain but with higher amounts of 2,3-di-sulfated alpha-units. The sulfated galactan from G. crinale has a lower anticoagulant activity on a clotting assay when compared with the polysaccharide from B. occidentalis. When tested in assays using specific proteases and coagulation inhibitors, these two galactans showed significant differences in their activity. They do not differ in thrombin inhibition mediated by antithrombin, but in assays where heparin cofactor II replaces antithrombin, the sulfated galactan from G. crinale requires a significantly higher concentration to achieve the same inhibitory effect as the polysaccharide from B. occidentalis. In contrast, when factor Xa instead of thrombin is used as the target protease, the sulfated galactan from G. crinale is a more potent anticoagulant. These observations suggest that the proportion and/or the distribution of 2,3-di-sulfated alpha-units along the galactan chain may be a critical structural motif to promote the interaction of the protease with specific protease and coagulation inhibitors.

Authors+Show Affiliations

Departamento de Bioquímica e Biologia Molecular, Universidade Federal do Ceará, 60455-760 Fortaleza, Ceará, Brazil.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

16023626

Citation

Pereira, Maria G., et al. "Structure and Anticoagulant Activity of a Sulfated Galactan From the Red Alga, Gelidium Crinale. Is There a Specific Structural Requirement for the Anticoagulant Action?" Carbohydrate Research, vol. 340, no. 12, 2005, pp. 2015-23.
Pereira MG, Benevides NM, Melo MR, et al. Structure and anticoagulant activity of a sulfated galactan from the red alga, Gelidium crinale. Is there a specific structural requirement for the anticoagulant action? Carbohydr Res. 2005;340(12):2015-23.
Pereira, M. G., Benevides, N. M., Melo, M. R., Valente, A. P., Melo, F. R., & Mourão, P. A. (2005). Structure and anticoagulant activity of a sulfated galactan from the red alga, Gelidium crinale. Is there a specific structural requirement for the anticoagulant action? Carbohydrate Research, 340(12), 2015-23.
Pereira MG, et al. Structure and Anticoagulant Activity of a Sulfated Galactan From the Red Alga, Gelidium Crinale. Is There a Specific Structural Requirement for the Anticoagulant Action. Carbohydr Res. 2005 Sep 5;340(12):2015-23. PubMed PMID: 16023626.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Structure and anticoagulant activity of a sulfated galactan from the red alga, Gelidium crinale. Is there a specific structural requirement for the anticoagulant action? AU - Pereira,Maria G, AU - Benevides,Norma M B, AU - Melo,Marcia R S, AU - Valente,Ana Paula, AU - Melo,Fábio R, AU - Mourão,Paulo A S, PY - 2005/04/04/received PY - 2005/05/28/accepted PY - 2005/7/19/pubmed PY - 2005/10/19/medline PY - 2005/7/19/entrez SP - 2015 EP - 23 JF - Carbohydrate research JO - Carbohydr Res VL - 340 IS - 12 N2 - Marine red algae are an abundant source of sulfated galactans with potent anticoagulant activity. However, the specific structural motifs that confer biological activity remain to be elucidated. We have now isolated and purified a sulfated galactan from the marine red alga, Gellidium crinale. The structure of this polysaccharide was determined using NMR spectroscopy. It is composed of the repeating structure -4-alpha-Galp-(1-->3)-beta-Galp1--> but with a variable sulfation pattern. Clearly 15% of the total alpha-units are 2,3-di-sulfated and another 55% are 2-sulfated. No evidence for the occurrence of 3,6-anhydro alpha-galactose units was observed in the NMR spectra. We also compared the anticoagulant activity of this sulfated galactan with a polysaccharide from the species, Botryocladia occidentalis, with a similar saccharide chain but with higher amounts of 2,3-di-sulfated alpha-units. The sulfated galactan from G. crinale has a lower anticoagulant activity on a clotting assay when compared with the polysaccharide from B. occidentalis. When tested in assays using specific proteases and coagulation inhibitors, these two galactans showed significant differences in their activity. They do not differ in thrombin inhibition mediated by antithrombin, but in assays where heparin cofactor II replaces antithrombin, the sulfated galactan from G. crinale requires a significantly higher concentration to achieve the same inhibitory effect as the polysaccharide from B. occidentalis. In contrast, when factor Xa instead of thrombin is used as the target protease, the sulfated galactan from G. crinale is a more potent anticoagulant. These observations suggest that the proportion and/or the distribution of 2,3-di-sulfated alpha-units along the galactan chain may be a critical structural motif to promote the interaction of the protease with specific protease and coagulation inhibitors. SN - 0008-6215 UR - https://www.unboundmedicine.com/medline/citation/16023626/Structure_and_anticoagulant_activity_of_a_sulfated_galactan_from_the_red_alga_Gelidium_crinale__Is_there_a_specific_structural_requirement_for_the_anticoagulant_action DB - PRIME DP - Unbound Medicine ER -