Skip Navigation



Glycobiology Advance Access published online on December 8, 2004
Glycobiology, doi:10.1093/glycob/cwi021
This Article
Right arrow Advance Access manuscript (PDF) Freely available
Right arrow Correction to PDF
Right arrow All Versions of this Article:
15/4/369    most recent
cwi021v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Pomin, V. H.
Right arrow Articles by Mouro, P. A.S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Pomin, V. H.
Right arrow Articles by Mouro, P. A.S.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© Oxford University Press 2004; all rights reserved.
Received September 16, 2004
Revised November 30, 2004
Accepted December 2, 2004

Article

Selective cleavage and anticoagulant activity of a sulfated fucan: Stereospecific removal of a 2-sulfate ester from the polysaccharide by mild acid hydrolysis, preparation of oligosaccharides and heparin cofactor II-dependent anticoagulant activity

Vitor H. Pomin 1, Mariana S. Pereira 2, Ana-Paula Valente 3, Douglas M. Tollefsen 4, Mauro S.G. Pavo 1, and Paulo A.S. Mouro 1*

1 Laboratório de Tecido Conjuntivo, Hospital Universitrio Clementino Fraga Filho,; Instituto de Bioquímica Médica,
2 Laboratório de Tecido Conjuntivo, Hospital Universitrio Clementino Fraga Filho,; Instituto de Ciências Biomédicas,
3 Instituto de Bioquímica Médica,; Centro Nacional de Ressonância Nuclear Magnética de Macromoléculas, Universidade Federal do Rio de Janeiro, Caixa Postal 68041, Rio de Janeiro, RJ, 21941-590, Brazil and
4 Division of Hematology, Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri, 63110, USA

* To whom correspondence should be addressed.
Paulo A.S. Mouro, E-mail: pmourao{at}hucff.ufrj.br.


  Abstract

A linear sulfated fucan with a regular repeating sequence of [3)-{alpha}-L-Fucp-(2SO4)- (1->3)-{alpha}-L-Fucp-(4SO4)-(1->3)-{alpha}-L-Fucp-(2,4SO4)-(1->3)-{alpha}-L-Fucp-(2SO4)-(1->]n is an anticoagulant polysaccharide mainly due to thrombin inhibition mediated by heparin cofactor II. No specific enzymatic or chemical method is available for the preparation of tailored oligosaccharides from sulfated fucans. We now employed an apparently non-specific approach to cleave this polysaccharide based on mild hydrolysis with acid. Surprisingly, the linear sulfated fucan was cleaved by mild acid hydrolysis on an ordered sequence. Initially a 2-sulfate ester of the first fucose unit is selectively removed. Thereafter, the glycosidic linkage between the nonsulfated fucose residue and the subsequent 4-sulfated residue is preferentially cleaved by acid hydrolysis, forming oligosaccharides with well-defined size. The low-molecular-weight derivatives obtained from the sulfated fucan were employed to determine the requirement for interaction of this polysaccharide with heparin cofactor II and to achieve complete thrombin inhibition. The linear sulfated fucan requires significantly longer chains than mammalian glycosaminoglycans to achieve anticoagulant activity. A slight decrease in the molecular size of the sulfated fucan dramatically reduces its effect on thrombin inactivation mediated by heparin cofactor II. Sulfated fucan with ~45 tetrasaccharide repeating units binds to heparin cofactor II but is unable to link efficiently the plasma inhibitor and thrombin. This last effect requires chains with ~100 or more tetrasaccharide repeating units. We speculate that the template mechanism may predominate over the allosteric effect in the case of the linear sulfated fucan inactivation of thrombin in the presence of heparin cofactor II.

Keywords: Sulfated fucans/stereospecific desulfation/selective cleavage of sulfated polysaccharide/anticoagulant activity/heparin cofactor II.
Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 J. Biol. Chem.Home page
M. O. Castro, V. H. Pomin, L. L. Santos, A.-C. E. S. Vilela-Silva, N. Hirohashi, L. Pol-Fachin, H. Verli, and P. A. S. Mourao
A Unique 2-Sulfated {beta}-Galactan from the Egg Jelly of the Sea Urchin Glyptocidaris crenularis: CONFORMATION FLEXIBILITY VERSUS INDUCTION OF THE SPERM ACROSOME REACTION
J. Biol. Chem., July 10, 2009; 284(28): 18790 - 18800.
[Abstract] [Full Text] [PDF]

Home page
 GlycobiologyHome page
V. H Pomin and P. A S Mourao
Structure, biology, evolution, and medical importance of sulfated fucans and galactans
Glycobiology, December 1, 2008; 18(12): 1016 - 1027.
[Abstract] [Full Text] [PDF]

Home page
 GlycobiologyHome page
E. H C Farias, V. H Pomin, A.-P. Valente, H. B Nader, H. A O Rocha, and P. A S Mourao
A preponderantly 4-sulfated, 3-linked galactan from the green alga Codium isthmocladum
Glycobiology, March 1, 2008; 18(3): 250 - 259.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
S. Prasad, D. Lillicrap, A. Labelle, S. Knappe, T. Keller, E. Burnett, S. Powell, and K. W. Johnson
Efficacy and safety of a new-class hemostatic drug candidate, AV513, in dogs with hemophilia A
Blood, January 15, 2008; 111(2): 672 - 679.
[Abstract] [Full Text] [PDF]

Home page
 GlycobiologyHome page
A. Cumashi, N. A. Ushakova, M. E. Preobrazhenskaya, A. D'Incecco, A. Piccoli, L. Totani, N. Tinari, G. E. Morozevich, A. E. Berman, M. I. Bilan, et al.
A comparative study of the anti-inflammatory, anticoagulant, antiangiogenic, and antiadhesive activities of nine different fucoidans from brown seaweeds
Glycobiology, May 1, 2007; 17(5): 541 - 552.
[Abstract] [Full Text] [PDF]

Home page
 GlycobiologyHome page
V. H. Pomin, A. P. Valente, M. S. Pereira, and P. A.S. Mourao
Mild acid hydrolysis of sulfated fucans: a selective 2-desulfation reaction and an alternative approach for preparing tailored sulfated oligosaccharides
Glycobiology, December 1, 2005; 15(12): 1376 - 1385.
[Abstract] [Full Text] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.