Anticoagulant and Antithrombotic Properties of Three Structurally Correlated Sea Urchin Sulfated Glycans and Their Low-Molecular-Weight Derivatives

The anticoagulant and antithrombotic properties of three structurally correlated sea urchin-derived 3-linked sulfated α-glycans and their low molecular-weight derivatives were screened comparatively through various in vitro and in vivo methods. These methods include activated partial throm...

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Main Authors: Ariana A. Vasconcelos, Isabela D. Sucupira, Alessandra L. Guedes, Ismael N. Queiroz, Flavia S. Frattani, Roberto J. Fonseca, Vitor H. Pomin
Format: Article
Language:English
Published: MDPI AG 2018-08-01
Series:Marine Drugs
Subjects:
Online Access:http://www.mdpi.com/1660-3397/16/9/304
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author Ariana A. Vasconcelos
Isabela D. Sucupira
Alessandra L. Guedes
Ismael N. Queiroz
Flavia S. Frattani
Roberto J. Fonseca
Vitor H. Pomin
author_facet Ariana A. Vasconcelos
Isabela D. Sucupira
Alessandra L. Guedes
Ismael N. Queiroz
Flavia S. Frattani
Roberto J. Fonseca
Vitor H. Pomin
author_sort Ariana A. Vasconcelos
collection DOAJ
description The anticoagulant and antithrombotic properties of three structurally correlated sea urchin-derived 3-linked sulfated α-glycans and their low molecular-weight derivatives were screened comparatively through various in vitro and in vivo methods. These methods include activated partial thromboplastin time, the inhibitory activity of antithrombin over thrombin and factor Xa, venous antithrombosis, the inhibition of platelet aggregation, the activation of factor XII, and bleeding. While the 2-sulfated fucan from Strongylocentrotus franciscanus was observed to be poorly active in most assays, the 4-sulfated fucan from Lytechinus variegatus, the 2-sulfated galactan from Echinometra lucunter and their derivatives showed multiple effects. All marine compounds showed no capacity to activate factor XII and similar low bleeding tendencies regardless of the dose concentrations used to achieve the highest antithrombotic effect observed. The 2-sulfated galactan showed the best combination of results. Our work improves the background about the structure-function relationship of the marine sulfated glycans in anticoagulation and antithrombosis. Besides confirming the negative effect of the 2-sulfated fucose and the positive effect of the 2-sulfated galactose on anticoagulation in vitro, our results also demonstrate the importance of this set of structural requirements on antithrombosis in vivo, and further support the involvement of high-molecular weight and 4-sulfated fucose in both activities.
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spelling doaj.art-4f380a2afd1243e48de47a7f293afad32022-12-22T04:27:19ZengMDPI AGMarine Drugs1660-33972018-08-0116930410.3390/md16090304md16090304Anticoagulant and Antithrombotic Properties of Three Structurally Correlated Sea Urchin Sulfated Glycans and Their Low-Molecular-Weight DerivativesAriana A. Vasconcelos0Isabela D. Sucupira1Alessandra L. Guedes2Ismael N. Queiroz3Flavia S. Frattani4Roberto J. Fonseca5Vitor H. Pomin6Program of Glycobiology, Institute of Medical Biochemistry Leopoldo de Meis, Federal University of Rio de Janeiro, Rio de Janeiro 21941-590, RJ, BrazilProgram of Glycobiology, Institute of Medical Biochemistry Leopoldo de Meis, Federal University of Rio de Janeiro, Rio de Janeiro 21941-590, RJ, BrazilProgram of Glycobiology, Institute of Medical Biochemistry Leopoldo de Meis, Federal University of Rio de Janeiro, Rio de Janeiro 21941-590, RJ, BrazilProgram of Glycobiology, Institute of Medical Biochemistry Leopoldo de Meis, Federal University of Rio de Janeiro, Rio de Janeiro 21941-590, RJ, BrazilDepartment of Clinical Analyses and Toxicology, School of Pharmacy, Federal University of Rio de Janeiro, Rio de Janeiro 21941-599, RJ, BrazilUniversity Hospital Clementino Fraga Filho, Federal University of Rio de Janeiro, Rio de Janeiro 21941-913, RJ, BrazilProgram of Glycobiology, Institute of Medical Biochemistry Leopoldo de Meis, Federal University of Rio de Janeiro, Rio de Janeiro 21941-590, RJ, BrazilThe anticoagulant and antithrombotic properties of three structurally correlated sea urchin-derived 3-linked sulfated α-glycans and their low molecular-weight derivatives were screened comparatively through various in vitro and in vivo methods. These methods include activated partial thromboplastin time, the inhibitory activity of antithrombin over thrombin and factor Xa, venous antithrombosis, the inhibition of platelet aggregation, the activation of factor XII, and bleeding. While the 2-sulfated fucan from Strongylocentrotus franciscanus was observed to be poorly active in most assays, the 4-sulfated fucan from Lytechinus variegatus, the 2-sulfated galactan from Echinometra lucunter and their derivatives showed multiple effects. All marine compounds showed no capacity to activate factor XII and similar low bleeding tendencies regardless of the dose concentrations used to achieve the highest antithrombotic effect observed. The 2-sulfated galactan showed the best combination of results. Our work improves the background about the structure-function relationship of the marine sulfated glycans in anticoagulation and antithrombosis. Besides confirming the negative effect of the 2-sulfated fucose and the positive effect of the 2-sulfated galactose on anticoagulation in vitro, our results also demonstrate the importance of this set of structural requirements on antithrombosis in vivo, and further support the involvement of high-molecular weight and 4-sulfated fucose in both activities.http://www.mdpi.com/1660-3397/16/9/304anticoagulationantithrombosismarine glycansulfated fucansulfated galactan
spellingShingle Ariana A. Vasconcelos
Isabela D. Sucupira
Alessandra L. Guedes
Ismael N. Queiroz
Flavia S. Frattani
Roberto J. Fonseca
Vitor H. Pomin
Anticoagulant and Antithrombotic Properties of Three Structurally Correlated Sea Urchin Sulfated Glycans and Their Low-Molecular-Weight Derivatives
Marine Drugs
anticoagulation
antithrombosis
marine glycan
sulfated fucan
sulfated galactan
title Anticoagulant and Antithrombotic Properties of Three Structurally Correlated Sea Urchin Sulfated Glycans and Their Low-Molecular-Weight Derivatives
title_full Anticoagulant and Antithrombotic Properties of Three Structurally Correlated Sea Urchin Sulfated Glycans and Their Low-Molecular-Weight Derivatives
title_fullStr Anticoagulant and Antithrombotic Properties of Three Structurally Correlated Sea Urchin Sulfated Glycans and Their Low-Molecular-Weight Derivatives
title_full_unstemmed Anticoagulant and Antithrombotic Properties of Three Structurally Correlated Sea Urchin Sulfated Glycans and Their Low-Molecular-Weight Derivatives
title_short Anticoagulant and Antithrombotic Properties of Three Structurally Correlated Sea Urchin Sulfated Glycans and Their Low-Molecular-Weight Derivatives
title_sort anticoagulant and antithrombotic properties of three structurally correlated sea urchin sulfated glycans and their low molecular weight derivatives
topic anticoagulation
antithrombosis
marine glycan
sulfated fucan
sulfated galactan
url http://www.mdpi.com/1660-3397/16/9/304
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