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Conformation of sulfated galactan and sulfated fucan in aqueous solutions: implications to their anticoagulant activities.
J Mol Graph Model. 2007 Jul; 26(1):391-9.JM

Abstract

The discovery of sulfated galactans and sulfated fucans in marine invertebrates with simple and ordered structures opened new perspectives to investigate the biological activity of these molecules and to determine whether different structures confer high affinity for a particular protein. We undertook a conformational analysis of a 2-sulfated, 3-linked alpha-L-galactan and of a alpha-L-fucan with similar structure. Through comparison between theoretical and NMR derived coupling constants, we observed that the pyranose rings are predominantly in the (1)C(4) conformation in these polysaccharides. Additionally, the geometry of the glycosidic linkages was determined based on force field calculations, indicating that the two polysaccharides have similar conformations in solution. Since the sulfated alpha-L-galactan, but not the alpha-L-fucan potentiates antithrombin (AT) inhibition of thrombin, the solution conformations of the compounds were docked into AT and the complexes obtained were refined through molecular dynamics calculations. The obtained results indicates extremely different orientations for the two polysaccharides, which well correlates and explain their distinct anticoagulant activities. Finally, the molecular mechanism of a selective 2-desulfation reaction, observed among sulfated fucans, was explained as a consequence of an intramolecular hydrogen bond capable of assisting in the removal of the charged group.

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Authors+Show Affiliations

Becker CF
Centro de Biotecnologia, Universidade Federal do Rio Grande do Sul, Av Bento Gonçalves 9500, CP 15005, Porto Alegre 91500-970, Brazil.
Guimarães JA
No affiliation info available
Mourão PA
No affiliation info available
Verli H
No affiliation info available

MeSH

AnimalsAnticoagulantsAntithrombinsCarbohydrate ConformationComputer SimulationGalactansHydrogen BondingHydrolysisIn Vitro TechniquesMacromolecular SubstancesModels, MolecularNuclear Magnetic Resonance, BiomolecularPolysaccharidesSoftwareSolutionsThermodynamicsWater

Pub Type(s)

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

Language

eng

PubMed ID

17307002

Citation

Becker, Camila F., et al. "Conformation of Sulfated Galactan and Sulfated Fucan in Aqueous Solutions: Implications to Their Anticoagulant Activities." Journal of Molecular Graphics & Modelling, vol. 26, no. 1, 2007, pp. 391-9.
Becker CF, Guimarães JA, Mourão PA, et al. Conformation of sulfated galactan and sulfated fucan in aqueous solutions: implications to their anticoagulant activities. J Mol Graph Model. 2007;26(1):391-9.
Becker, C. F., Guimarães, J. A., Mourão, P. A., & Verli, H. (2007). Conformation of sulfated galactan and sulfated fucan in aqueous solutions: implications to their anticoagulant activities. Journal of Molecular Graphics & Modelling, 26(1), 391-9.
Becker CF, et al. Conformation of Sulfated Galactan and Sulfated Fucan in Aqueous Solutions: Implications to Their Anticoagulant Activities. J Mol Graph Model. 2007;26(1):391-9. PubMed PMID: 17307002.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Conformation of sulfated galactan and sulfated fucan in aqueous solutions: implications to their anticoagulant activities. AU - Becker,Camila F, AU - Guimarães,Jorge A, AU - Mourão,Paulo A S, AU - Verli,Hugo, Y1 - 2007/01/19/ PY - 2006/11/22/received PY - 2007/01/13/revised PY - 2007/01/15/accepted PY - 2007/2/20/pubmed PY - 2007/10/12/medline PY - 2007/2/20/entrez SP - 391 EP - 9 JF - Journal of molecular graphics & modelling JO - J Mol Graph Model VL - 26 IS - 1 N2 - The discovery of sulfated galactans and sulfated fucans in marine invertebrates with simple and ordered structures opened new perspectives to investigate the biological activity of these molecules and to determine whether different structures confer high affinity for a particular protein. We undertook a conformational analysis of a 2-sulfated, 3-linked alpha-L-galactan and of a alpha-L-fucan with similar structure. Through comparison between theoretical and NMR derived coupling constants, we observed that the pyranose rings are predominantly in the (1)C(4) conformation in these polysaccharides. Additionally, the geometry of the glycosidic linkages was determined based on force field calculations, indicating that the two polysaccharides have similar conformations in solution. Since the sulfated alpha-L-galactan, but not the alpha-L-fucan potentiates antithrombin (AT) inhibition of thrombin, the solution conformations of the compounds were docked into AT and the complexes obtained were refined through molecular dynamics calculations. The obtained results indicates extremely different orientations for the two polysaccharides, which well correlates and explain their distinct anticoagulant activities. Finally, the molecular mechanism of a selective 2-desulfation reaction, observed among sulfated fucans, was explained as a consequence of an intramolecular hydrogen bond capable of assisting in the removal of the charged group. SN - 1093-3263 UR - https://www.unboundmedicine.com/medline/citation/17307002/Conformation_of_sulfated_galactan_and_sulfated_fucan_in_aqueous_solutions:_implications_to_their_anticoagulant_activities_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1093-3263(07)00009-5 DB - PRIME DP - Unbound Medicine ER -