Synthesis and anticoagulant activity of glycosaminoglycan copolymers

last updated: 2017-11-21
ProjectCHEM2NATURE :: publications list
TitleSynthesis and anticoagulant activity of glycosaminoglycan copolymers
Publication TypeComunications - Poster
Year of Publication2017
AuthorsGomes M., Lozano-Fernández T., Gallego A., Gonzalez-Fernández A., Reis R. L., Novoa-Carballal R., and Pashkuleva I.

Glycosaminoglycans (GAGs) are one of the main building elements of the pericellular space, where they can either determine the physical characteristics of tissues or modulate the biological functions of cells by their involvement in different cell signaling pathways, including the inflammation and coagulation cascades [1-2]. Because of their diverse bioactivities proteoglycans (PGs) have been suggested as therapeutics for various diseases including thrombosis [3]. The difficulties in PG isolation and purification have encouraged the development of biomimicking glycopolymers, glycodendrimers and nanoparticles that comprises synthetic polymers with different architectures and carbohydrates [3]. Nevertheless, in the vast majority of procedures, the carbohydrate portion is limited to mono- or oligosaccharides that are too short to resemble the multivalent interactions of GAGs. Moreover, the attachment mode (side-on) can obstruct GAG’s bioactivity. In this work, we show an alternative approach in which GAGs (chondroitin sulfate and heparin) with longer chains (molecular weight up to 14 kDa) are attached via their reducing end to hydroxyethyl methacrylate or hyperbranched polyglycerol by end-on oxime ligation. We prove that the acquired glycomimics have preserved GAGs bioactivity. Indeed, after the incubation with human plasma, star-like heparin copolymers increased clotting time in all the tests performed (Thrombin, Prothrombin and Activated Partial thromboplastin time), which demonstrates a strong anticoagulant activity. These outcomes indicate that the obtained glycomimics can be used as substitute to natural PGs due to a closer mimic of the natural structures.

Conference NameInternational Symposium on Bioinspired Macromolecular Systems
Date Published2017-11-06
Conference LocationAveiro
Keywordsanticoagulant activity, copolymers, Glycosaminoglycans
Peer reviewedno

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