{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T21:58:10Z","timestamp":1782338290319,"version":"3.54.5"},"reference-count":36,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2018,8,30]],"date-time":"2018-08-30T00:00:00Z","timestamp":1535587200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["Universal 442311\/2014-1"],"award-info":[{"award-number":["Universal 442311\/2014-1"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Marine Drugs"],"abstract":"<jats:p>The anticoagulant and antithrombotic properties of three structurally correlated sea urchin-derived 3-linked sulfated \u03b1-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.<\/jats:p>","DOI":"10.3390\/md16090304","type":"journal-article","created":{"date-parts":[[2018,8,30]],"date-time":"2018-08-30T10:30:06Z","timestamp":1535625006000},"page":"304","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Anticoagulant and Antithrombotic Properties of Three Structurally Correlated Sea Urchin Sulfated Glycans and Their Low-Molecular-Weight Derivatives"],"prefix":"10.3390","volume":"16","author":[{"given":"Ariana A.","family":"Vasconcelos","sequence":"first","affiliation":[{"name":"Program of Glycobiology, Institute of Medical Biochemistry Leopoldo de Meis, Federal University of Rio de Janeiro, Rio de Janeiro 21941-590, RJ, Brazil"},{"name":"University Hospital Clementino Fraga Filho, Federal University of Rio de Janeiro, Rio de Janeiro 21941-913, RJ, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabela D.","family":"Sucupira","sequence":"additional","affiliation":[{"name":"Program of Glycobiology, Institute of Medical Biochemistry Leopoldo de Meis, Federal University of Rio de Janeiro, Rio de Janeiro 21941-590, RJ, Brazil"},{"name":"University Hospital Clementino Fraga Filho, Federal University of Rio de Janeiro, Rio de Janeiro 21941-913, RJ, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra L.","family":"Guedes","sequence":"additional","affiliation":[{"name":"Program of Glycobiology, Institute of Medical Biochemistry Leopoldo de Meis, Federal University of Rio de Janeiro, Rio de Janeiro 21941-590, RJ, Brazil"},{"name":"Department of Clinical Analyses and Toxicology, School of Pharmacy, Federal University of Rio de Janeiro, Rio de Janeiro 21941-599, RJ, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ismael N.","family":"Queiroz","sequence":"additional","affiliation":[{"name":"Program of Glycobiology, Institute of Medical Biochemistry Leopoldo de Meis, Federal University of Rio de Janeiro, Rio de Janeiro 21941-590, RJ, Brazil"},{"name":"University Hospital Clementino Fraga Filho, Federal University of Rio de Janeiro, Rio de Janeiro 21941-913, RJ, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Flavia S.","family":"Frattani","sequence":"additional","affiliation":[{"name":"Department of Clinical Analyses and Toxicology, School of Pharmacy, Federal University of Rio de Janeiro, Rio de Janeiro 21941-599, RJ, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto J.","family":"Fonseca","sequence":"additional","affiliation":[{"name":"University Hospital Clementino Fraga Filho, Federal University of Rio de Janeiro, Rio de Janeiro 21941-913, RJ, Brazil"},{"name":"Undergraduate Program in Pharmacology, Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de Janeiro 21941-902, RJ, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5015-8880","authenticated-orcid":false,"given":"Vitor H.","family":"Pomin","sequence":"additional","affiliation":[{"name":"Program of Glycobiology, Institute of Medical Biochemistry Leopoldo de Meis, Federal University of Rio de Janeiro, Rio de Janeiro 21941-590, RJ, Brazil"},{"name":"University Hospital Clementino Fraga Filho, Federal University of Rio de Janeiro, Rio de Janeiro 21941-913, RJ, Brazil"},{"name":"Department of BioMolecular Sciences, Division of Pharmacognosy, and Research Institute of Pharmaceutical Sciences, School of Pharmacy, University of Mississippi, Oxford, MS 38677-1848, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2018,8,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2363","DOI":"10.1161\/ATVBAHA.114.304488","article-title":"Thrombosis: A major contributor to global disease burden","volume":"34","author":"Raskob","year":"2014","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_2","unstructured":"(2018, July 15). The Top 10 Causes of Death. Available online: http:\/\/www.who.int\/mediacentre\/factsheets\/fs310\/en\/."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"S29","DOI":"10.1016\/j.thromres.2008.08.010","article-title":"Brave new world: The current and future use of novel anticoagulants","volume":"123","author":"Spyropoulos","year":"2008","journal-title":"Thromb. Res."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"116","DOI":"10.3109\/07853890.2010.539250","article-title":"Old and new anticoagulant drugs: A minireview","volume":"43","author":"Mannucci","year":"2011","journal-title":"Ann. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1465","DOI":"10.1016\/j.amjcard.2007.06.041","article-title":"Adverse drug events in hospitalized cardiac patients","volume":"100","author":"Fanikos","year":"2007","journal-title":"Am. J. Cardiol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1752","DOI":"10.1001\/archinte.167.16.1752","article-title":"Serious adverse drug events reported to the Food and Drug Administration, 1998\u20132005","volume":"167","author":"Moore","year":"2007","journal-title":"Arch. Intern. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1124\/pr.115.011247","article-title":"Pharmacology of heparin and related drugs","volume":"68","author":"Mulloy","year":"2016","journal-title":"Pharmacol. Rev."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1136\/pgmj.2007.059188","article-title":"Heparin induced thrombocytopenia: Diagnosis and management update","volume":"83","author":"Ahmed","year":"2007","journal-title":"Postgrad. Med. J."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"e355","DOI":"10.1161\/CIRCULATIONAHA.106.632653","article-title":"Heparin-induced thrombocytopenia","volume":"114","author":"Baroletti","year":"2006","journal-title":"Circulation"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1212\/WNL.34.1.114","article-title":"Heparin therapy for stroke: Hemorrhagic complications and risk factors for intracerebral hemorrhage","volume":"34","author":"Quinones","year":"1984","journal-title":"Neurology"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"872","DOI":"10.1161\/01.STR.22.7.872","article-title":"Cerebral hemorrhagic risk of aspirin or heparin therapy with thrombolytic treatment in rabbits","volume":"22","author":"Clark","year":"1991","journal-title":"Stroke"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1971","DOI":"10.1016\/j.bbagen.2012.08.022","article-title":"Fucanomics and galactanomics: Current status in drug discovery, mechanisms of action and role of the well-defined structures","volume":"1820","author":"Pomin","year":"2012","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"848","DOI":"10.3390\/ph8040848","article-title":"Marine non-glycosaminoglycan sulfated glycans as potential pharmaceuticals","volume":"8","author":"Pomin","year":"2015","journal-title":"Pharmaceuticals"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1195","DOI":"10.1002\/med.21356","article-title":"A dilemma in the glycosaminoglycan-based therapy: Synthetic or naturally unique molecules?","volume":"35","author":"Pomin","year":"2015","journal-title":"Med. Res. Rev."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"232","DOI":"10.3390\/md12010232","article-title":"Holothurian fucosylated chondroitin sulfate","volume":"12","author":"Pomin","year":"2014","journal-title":"Mar. Drugs"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"4166","DOI":"10.2174\/0929867322666151020101335","article-title":"Medical gains of chondroitin sulfate upon fucosylation","volume":"22","author":"Pomin","year":"2015","journal-title":"Curr. Med. Chem."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2231","DOI":"10.1016\/S0008-6215(02)00215-X","article-title":"A 2-sulfated, 3-linked \u03b1-L-galactan is an anticoagulant polysaccharide","volume":"337","author":"Pereira","year":"2002","journal-title":"Carbohydr. Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1093\/glycob\/cwf077","article-title":"Is there a correlation between structure and anticoagulant action of sulfated galactans and sulfated fucans?","volume":"12","author":"Pereira","year":"2002","journal-title":"Glycobiology"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1160\/TH08-11-0773","article-title":"Effects of polysaccharides enriched in 2,4-disulfated fucose units on coagulation, thrombosis and bleeding. Practical and conceptual implications","volume":"102","author":"Fonseca","year":"2009","journal-title":"Thromb. Haemost."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"822","DOI":"10.1160\/TH06-06-0304","article-title":"Fucosylated chondroitin sulfate as a new oral antithrombotic agent","volume":"96","author":"Fonseca","year":"2006","journal-title":"Thromb. Haemost."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"662","DOI":"10.1160\/TH16-09-0694","article-title":"Improved anticoagulant effect of fucosylated chondroitin sulfate orally administered as gastro-resistant tablets","volume":"117","author":"Fonseca","year":"2017","journal-title":"Thromb. Haemost."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"877","DOI":"10.1093\/glycob\/cwm058","article-title":"Expression of two different sulfated fucans by females of Lytechinus variegatus may regulate the seasonal variation in the fertilization of the sea urchin","volume":"17","author":"Cinelli","year":"2007","journal-title":"Glycobiology"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"927","DOI":"10.1093\/glycob\/9.9.927","article-title":"Structure of the sulfated alpha-L-fucan from the egg jelly coat of the sea urchin Strongylocentrotus franciscanus: Patterns of preferential 2-O- and 4-O-sulfation determine sperm cell recognition","volume":"9","author":"Alves","year":"1999","journal-title":"Glycobiology"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"6965","DOI":"10.1074\/jbc.272.11.6965","article-title":"Sulfated polysaccharides from the egg jelly layer are species-specific inducers of acrosomal reaction in sperms of sea urchins","volume":"272","author":"Alves","year":"1997","journal-title":"J. Biol. Chem."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1093\/glycob\/cwu184","article-title":"Impact of sulfation pattern on the conformation and dynamics of sulfated fucan oligosaccharides as revealed by NMR and MD","volume":"25","author":"Queiroz","year":"2015","journal-title":"Glycobiology"},{"key":"ref_26","first-page":"1257","article-title":"Oligosaccharides from the 3-linked 2-sulfated alpha-L-fucan and alpha-l-galactan show similar conformations but different dynamics","volume":"26","author":"Queiroz","year":"2016","journal-title":"Glycobiology"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1007\/s10719-014-9530-1","article-title":"Anticoagulant motifs of marine sulfated glycans","volume":"31","author":"Pomin","year":"2014","journal-title":"Glycoconj. J."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1111\/jth.12448","article-title":"Is the antithrombotic effect of sulfated galactans independent of serpin?","volume":"12","author":"Santos","year":"2014","journal-title":"J. Thromb. Haemost."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1160\/TH07-10-0649","article-title":"An algal sulfated galactan has an unusual dual effect on venous thrombosis due to activation of factor XII and inhibition of the coagulation proteases","volume":"99","author":"Melo","year":"2008","journal-title":"Thromb. Haemost."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"3965","DOI":"10.1016\/j.bmc.2016.07.037","article-title":"Dual and antagonic therapeutic effects of sulfated glycans","volume":"24","author":"Pomin","year":"2016","journal-title":"Bioorg. Med. Chem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"994","DOI":"10.1160\/TH09-10-0734","article-title":"Effects of oversulfated and fucosylated chondroitin sulfates on coagulation. Challenges for the study of anticoagulant polysaccharides","volume":"103","author":"Fonseca","year":"2010","journal-title":"Thromb. Haemost."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1093\/glycob\/cwi021","article-title":"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","volume":"15","author":"Pomin","year":"2005","journal-title":"Glycobiology"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"943","DOI":"10.1152\/jappl.1959.14.6.943","article-title":"Biologic assay of a thrombosis-inducing activity in human serum","volume":"14","author":"Wessler","year":"1959","journal-title":"J. Appl. Physiol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2281","DOI":"10.1182\/blood.V80.9.2281.bloodjournal8092281","article-title":"Importance of platelets in experimental venous thrombosis in the rat","volume":"80","author":"Herbert","year":"1992","journal-title":"Blood"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1160\/TH07-10-0603","article-title":"Slight differences in sulfation of algal galactans account for differences in their anticoagulant and venous antithrombotic activities","volume":"99","author":"Fonseca","year":"2008","journal-title":"Thromb. Haemost."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1016\/j.jmgm.2007.01.008","article-title":"Conformation of sulfated galactan and sulfated fucan in aqueous solutions: Implications to their anticoagulant activities","volume":"26","author":"Becker","year":"2007","journal-title":"J. Mol. Graph. Model."}],"container-title":["Marine Drugs"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1660-3397\/16\/9\/304\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T15:22:04Z","timestamp":1760196124000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1660-3397\/16\/9\/304"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,8,30]]},"references-count":36,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2018,9]]}},"alternative-id":["md16090304"],"URL":"https:\/\/doi.org\/10.3390\/md16090304","relation":{},"ISSN":["1660-3397"],"issn-type":[{"value":"1660-3397","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,8,30]]}}}