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 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

Skin tissue engineering using functional marine biomaterials

International audienceThe development of new skin substitutes is based on the construction of a scaffold (such as films, hydrogels, plates, sheets, fibers, sponges). Numerous hydrogels are already used and the polymers, which are able to form hydrogels, are either from a natural origin (hyaluronic acid, alginate, chitosan, chondroitin sulfate, collagen, etc.) or from a synthetic one (polylactide-co-glycolic, polyethylene glycol, etc.). The therapeutic potential of natural bioactive compounds such as polysaccharides (especially glycosaminoglycans or GAGs) is now well documented, and this activity combined with their natural biodiversity will allow the development of a new generation of therapeutics. Marine environment can offer a large variety of GAG-like molecules from various origins (animals, seaweeds, invertebrates, microorganisms, etc.), which could be a good alternative to the use of mammalian GAGs as bioactive components for tissue regeneration. Recent studies have been made on newly described marine bacteria isolated from hydrothermal deep-sea vents and able to produce extracellular polysaccharides (EPS) with unusual structures. These bacterial EPS and their derivatives offer great advantages over both mammalian GAGs and other traditional marine polysaccharides. These biotechnologically produced marine GAG-like molecules and their derivatives present often very original structures and have a better benefit/risk ratio than GAGs from mammalian origins (e.g., heparin)

Heparin-like Entities from Marine Organisms

Polysaccharides are ubiquitous in animals and plant cells where they play a significant role in a number of physiological situations e.g. hydration, mechanical properties of cell walls and ionic regulation. This review concentrates on heparin-like entities from marine procaryotes and eukaryotes. Carbohydrates from marine prokaryotes offer a significant structural chemodiversity with novel material and biological properties. Cyanobacteria are Gram-negative photosynthetic prokaryotes considered as a rich source of novel molecules, and marine bacteria are a rich source of polysaccharides with novel structures, which may be a good starting point from which to synthesise heparinoid molecules. For example, some sulphated polysaccharides have been isolated from gamma-proteobacteria such as Alteromonas and Pseudoalteromonas sp. In contrast to marine bacteria, all marine algae contain sulphated wall polysaccharides, whereas such polymers are not found in terrestrial plants. In their native form, or after chemical modifications, a range of polysaccharides isolated from marine organisms have been described that have anticoagulant, anti-thrombotic, anti-tumour, anti-proliferative, anti-viral or anti-inflammatory activities. In spite of the enormous potential of sulphated oligosaccharides from marine sources, their technical and pharmaceutical usage is still limited because of the high complexity of these molecules. Thus, the production of tailor-made oligo- and polysaccharidic structures by biocatalysis is also a growing field of interest in biotechnology

Proteoglycans on bone tumor development

Proteoglycans, extracellular matrix components, exert several activities on bone cells and seem crucial for maintaining an appropriate number of osteoblasts and osteoclasts. The overall data strengthen a pro-bone resorptive role for proteoglycans, through the control of osteoprotegerin availability and of receptor activator of NF-κB ligand bioactivity. In parallel, proteoglycans participate in the control of tumor development at different levels, including bone tumor development and bone metastases dissemination. This dual role makes them good candidates as regulatory molecules in the vicious cycle between tumor proliferation and bone resorption observed during tumor development in bone site. Knowledge of the biological roles of these molecules in cancer biology, tumor angiogenesis and metastasis has promoted the development of drugs targeting them

Assessment of biochemical methods to detect enzymatic depolymerization of polysaccharides

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