Fucoidan‐Mimetic Glycopolymers as Tools for Studying Molecular and Cellular Responses in Human Blood Platelets

• Published in: Macromolecular bioscience 2017-02, Vol.17 (2), p.1600257-n/a
• Main Authors: Tengdelius, Mattias, Kardeby, Caroline, Fälker, Knut, Griffith, May, Påhlsson, Peter, Konradsson, Peter, Grenegård, Magnus
• Format: Article
• Language: English
• Subjects: Addition polymerization; Agglomeration; Amides; biological applications of polymers; biomimetic; Biomimetic Materials - chemistry; Biomimetic Materials - pharmacology; Blood; Blood platelets; Blood Platelets - cytology; Blood Platelets - drug effects; Cellular structure; Chain transfer; Flow Cytometry; Fucoidan; Glycopolymers; Heterogeneous structure; Human behavior; Humans; Intracellular signalling; Phosphorylation; Phosphorylation - drug effects; Phosphotyrosine - metabolism; Platelet aggregation; Platelet Aggregation - drug effects; Platelets; Polymerization; Polysaccharides; Polysaccharides - chemistry; Polysaccharides - pharmacology; Proton Magnetic Resonance Spectroscopy; radical polymerization; reversible addition fragmentation chain transfer; structure–property relations; Tyrosine
• ISSN: 1616-5187; 1616-5195; 1616-5195
• DOI: 10.1002/mabi.201600257

The marine sulfated polysaccharide fucoidan displays superior ability to induce platelet aggregation compared to other sulfated polysaccharides. As such, it is an attractive tool for studying molecular and cellular responses in activated platelets. The heterogeneous structure, however, poses a problem in such applications. This study describes the synthesis of sulfated α‐l‐fucoside‐pendant poly(methacryl amides) with homogeneous structures. By using both thiol‐mediated chain transfer and reversible addition‐fragmentation chain transfer polymerization techniques, glycopolymers with different chain lengths are obtained. These glycopolymers show platelet aggregation response and surface changes similar to those of fucoidan, and cause platelet activation through intracellular signaling as shown by extensive protein tyrosine phosphorylation. As the platelet activating properties of the glycopolymers strongly mimic those of fucoidan, this study concludes these fucoidan‐mimetic glycopolymers are unique tools for studying molecular and cellular responses in human blood platelets. The marine polysaccharide fucoidan offers unique platelet activating properties, but its heterogeneous structure poses an obstacle for studying the cellular and molecular responses in platelets. Homogeneous fucoidan‐mimetic glycopolymers of different chain lengths are therefore synthesized. These glycopolymers induce platelet aggregation and platelet surface changes similar to those of fucoidan and activate platelets through intracellular signaling.