Abstract
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 28 antithrombin and heparin cofactor II. Only highly sulfated derivatives significantly pro-29 longed activated partial thromboplastin time while showing negligible effect on throm-30 bin time and anti-factor Xa activity. They present different structures and their binding to 31 antithrombin is not achieved via the classic pentasaccharide motif. In TGA, these deriv-32 atives inhibited thrombin formation at higher doses than heparin but induced a marked 33 delay in clot generation. Docking analyses supported their ability to bind serpins, albeit 34 with lower specificity than heparin. Their limited anti-Xa activity and non-animal origin 35 position them as promising anticoagulant candidates.