Fucoidan-Mimetic Glycopolymers as Tools for Studying Molecular and Cellular Responses in Human Blood Platelets.
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.
Division of Organic Chemistry, Department of Physics, Biology and Chemistry (IFM), Linköping University, SE-581 83, Linköping, Sweden.
Mattias
M
Tengdelius
Cardiovascular Research Centre, School of Medical Sciences, Örebro University, SE-701 82, Örebro, Sweden.
Caroline
C
Kardeby
Cardiovascular Research Centre, School of Medical Sciences, Örebro University, SE-701 82, Örebro, Sweden.
Knut
K
Fälker
Division of Cell Biology, Department of Clinical and Experimental Medicine (IKE), Linköping University, SE-581 83, Linköping, Sweden.
May
M
Griffith
Division of Cell Biology, Department of Clinical and Experimental Medicine (IKE), Linköping University, SE-581 83, Linköping, Sweden.
Peter
P
Påhlsson
Division of Organic Chemistry, Department of Physics, Biology and Chemistry (IFM), Linköping University, SE-581 83, Linköping, Sweden.
Peter
P
Konradsson
Cardiovascular Research Centre, School of Medical Sciences, Örebro University, SE-701 82, Örebro, Sweden.
Magnus
M
Grenegård
D040761:Biomimetic Materials / Q000737:chemistry / Q000494:pharmacology*; D001792:Blood Platelets / Q000166:cytology* / Q000187:drug effects; D005434:Flow Cytometry; D006801:Humans; D010766:Phosphorylation / Q000187:drug effects; D019000:Phosphotyrosine / Q000378:metabolism; D010974:Platelet Aggregation / Q000187:drug effects; D058105:Polymerization; D011134:Polysaccharides / Q000737:chemistry / Q000494:pharmacology*; D066244:Proton Magnetic Resonance Spectroscopy
D011134:Polysaccharides; D019000:Phosphotyrosine; C007789:fucoidan
biological applications of polymers; biomimetic; radical polymerization; reversible addition fragmentation chain transfer; structure-property relations