Anticoagulant Potential of Modified Sulfated Exopolysaccharides from Deep-Sea Bacteria: Toward Non-Animal Heparin Alternatives
Heparin, a widely used polysaccharidic anticoagulant of animal origin, is associated with risks of contamination and adverse effects, notably bleeding and thrombocytopenia. These limitations have prompted interest in alternative sulfated polysaccharides with anticoagulant properties and improved saf...
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2025-06-01
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| author | Antoine Babuty Agata Zykwinska Sergey A. Samsonov Nathalie Candia Catherine Veinstein Martine Pugnière Thi Hong Giang Ngo Corinne Sinquin Javier Muñoz-Garcia Sylvia Colliec-Jouault Dominique Heymann |
| author_facet | Antoine Babuty Agata Zykwinska Sergey A. Samsonov Nathalie Candia Catherine Veinstein Martine Pugnière Thi Hong Giang Ngo Corinne Sinquin Javier Muñoz-Garcia Sylvia Colliec-Jouault Dominique Heymann |
| author_sort | Antoine Babuty |
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| description | Heparin, a widely used polysaccharidic anticoagulant of animal origin, is associated with risks of contamination and adverse effects, notably bleeding and thrombocytopenia. These limitations have prompted interest in alternative sulfated polysaccharides with anticoagulant properties and improved safety profiles. This study explored the anticoagulant potential of two marine bacterial exopolysaccharides (EPS), infernan and diabolican. It assessed whether chemical modifications (depolymerization, oversulfation) could enhance their anticoagulant properties compared to unfractionated and low molecular weight heparins. Native EPS were depolymerized to generate different molecular weights and then chemically oversulfated to increase negative charge density. Anticoagulant activities were evaluated using clotting and thrombin generation assays (TGA). Molecular docking was performed to model interactions with antithrombin and heparin cofactor II. Only highly sulfated derivatives significantly prolonged activated partial thromboplastin time while showing negligible effect on thrombin time and anti-factor Xa activity. They present different structures, and their binding to antithrombin is not achieved via the classic pentasaccharide motif. In TGA, these derivatives inhibited thrombin formation at higher doses than heparin but induced a marked delay in clot generation. Docking analyses supported their ability to bind serpins, albeit with lower specificity than heparin. Their limited anti-Xa activity and non-animal origin position them as promising anticoagulant candidates. |
| format | Article |
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| institution | Kabale University |
| issn | 2673-4176 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | MDPI AG |
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| series | Polysaccharides |
| spelling | doaj-art-e506adacc461479ca4e44d8064296bf22025-08-20T03:27:36ZengMDPI AGPolysaccharides2673-41762025-06-01625410.3390/polysaccharides6020054Anticoagulant Potential of Modified Sulfated Exopolysaccharides from Deep-Sea Bacteria: Toward Non-Animal Heparin AlternativesAntoine Babuty0Agata Zykwinska1Sergey A. Samsonov2Nathalie Candia3Catherine Veinstein4Martine Pugnière5Thi Hong Giang Ngo6Corinne Sinquin7Javier Muñoz-Garcia8Sylvia Colliec-Jouault9Dominique Heymann10CNRS, UMR6286, US2B, Nantes University, 44000 Nantes, FranceIFREMER, MASAE Microbiologie Aliment Santé Environnement, 44000 Nantes, FranceFaculty of Chemistry, Gdańsk University, 80233 Gdańsk, PolandService d’Hématologie Biologique, Nantes University Hospital, 44000 Nantes, FranceService d’Hématologie Biologique, Nantes University Hospital, 44000 Nantes, FranceINSERM, UMR 1194, IRCM, Montpellier University, 34000 Montpellier, FranceINSERM, UMR 1194, IRCM, Montpellier University, 34000 Montpellier, FranceIFREMER, MASAE Microbiologie Aliment Santé Environnement, 44000 Nantes, FranceCNRS, UMR6286, US2B, Nantes University, 44000 Nantes, FranceIFREMER, MASAE Microbiologie Aliment Santé Environnement, 44000 Nantes, FranceCNRS, UMR6286, US2B, Nantes University, 44000 Nantes, FranceHeparin, a widely used polysaccharidic anticoagulant of animal origin, is associated with risks of contamination and adverse effects, notably bleeding and thrombocytopenia. These limitations have prompted interest in alternative sulfated polysaccharides with anticoagulant properties and improved safety profiles. This study explored the anticoagulant potential of two marine bacterial exopolysaccharides (EPS), infernan and diabolican. It assessed whether chemical modifications (depolymerization, oversulfation) could enhance their anticoagulant properties compared to unfractionated and low molecular weight heparins. Native EPS were depolymerized to generate different molecular weights and then chemically oversulfated to increase negative charge density. Anticoagulant activities were evaluated using clotting and thrombin generation assays (TGA). Molecular docking was performed to model interactions with antithrombin and heparin cofactor II. Only highly sulfated derivatives significantly prolonged activated partial thromboplastin time while showing negligible effect on thrombin time and anti-factor Xa activity. They present different structures, and their binding to antithrombin is not achieved via the classic pentasaccharide motif. In TGA, these derivatives inhibited thrombin formation at higher doses than heparin but induced a marked delay in clot generation. Docking analyses supported their ability to bind serpins, albeit with lower specificity than heparin. Their limited anti-Xa activity and non-animal origin position them as promising anticoagulant candidates.https://www.mdpi.com/2673-4176/6/2/54marine bacteriaheparinexopolysaccharideanticoagulation |
| spellingShingle | Antoine Babuty Agata Zykwinska Sergey A. Samsonov Nathalie Candia Catherine Veinstein Martine Pugnière Thi Hong Giang Ngo Corinne Sinquin Javier Muñoz-Garcia Sylvia Colliec-Jouault Dominique Heymann Anticoagulant Potential of Modified Sulfated Exopolysaccharides from Deep-Sea Bacteria: Toward Non-Animal Heparin Alternatives Polysaccharides marine bacteria heparin exopolysaccharide anticoagulation |
| title | Anticoagulant Potential of Modified Sulfated Exopolysaccharides from Deep-Sea Bacteria: Toward Non-Animal Heparin Alternatives |
| title_full | Anticoagulant Potential of Modified Sulfated Exopolysaccharides from Deep-Sea Bacteria: Toward Non-Animal Heparin Alternatives |
| title_fullStr | Anticoagulant Potential of Modified Sulfated Exopolysaccharides from Deep-Sea Bacteria: Toward Non-Animal Heparin Alternatives |
| title_full_unstemmed | Anticoagulant Potential of Modified Sulfated Exopolysaccharides from Deep-Sea Bacteria: Toward Non-Animal Heparin Alternatives |
| title_short | Anticoagulant Potential of Modified Sulfated Exopolysaccharides from Deep-Sea Bacteria: Toward Non-Animal Heparin Alternatives |
| title_sort | anticoagulant potential of modified sulfated exopolysaccharides from deep sea bacteria toward non animal heparin alternatives |
| topic | marine bacteria heparin exopolysaccharide anticoagulation |
| url | https://www.mdpi.com/2673-4176/6/2/54 |
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