Fucoidan-Mimetic Glycopolymers : Synthesis and Biomedical Applications [thesis]

Mattias Tengdelius
Cover: 3D models of three different fucoidan-mimetic glycopolymers Till morfar som inspirerade mig att börja och Lina och Theo som inspirerar mig att fortsätta. Mattias Tengdelius Fucoidan-Mimetic Glycopolymers -Synthesis and Biomedical Applications I Abstract The marine polysaccharide fucoidan has demonstrated several interesting biological properties, for instance being antiviral, anticoagulant, anti-inflammatory, anticancer, and platelet activating. Many of these properties are desirable for
more » ... s are desirable for various biomedical applications. Yet, there are few reports on fucoidan being used in such applications. The reasons for this are primarily the heterogeneity and low structural reproducibility of fucoidan. This thesis describes the synthesis of polymers with pendant saccharides bearing the key structural features of fucoidan. These glycopolymers were synthesized via different radical polymerization techniques yielding polymers of different chain lengths and dispersity. These glycopolymers showed antiviral and platelet activating properties similar to those of natural fucoidan, thus making them fucoidan-mimetic glycopolymers. However, compared to fucoidan from natural sources, the fucoidan-mimetic glycopolymers had homogeneous and reproducible structures making them suitable for biomedical applications. Although mine is the only name appearing on the cover of this thesis, it would never have seen the light of day without the help and support of my supervisors, collaborators, colleagues, family and friends. You all helped me get through this in different ways and, although I sometimes struggled, it resulted in a thesis of which I am very proud. I would therefore like to extend my deepest of thanks to the following people: My main supervisor, Peter Konradsson, for helping me become a PhD student and providing the means necessary to make it all the way. Although we did not start with a full squad, the game was still won. My co-supervisor, May Griffith, for always being supportive and believing in this project and my ideas. My co-supervisor, Peter Påhlsson, for always being supportive and helpful. You showed me the right direction when everything felt the most difficult. My original main supervisor, Bo Liedberg, for guiding me in my early days as a PhD student and helping me prioritize. Jöns Hilborn, for always being helpful and making me understand the field of polymer chemistry. The short time I spent in Uppsala was instrumental to the work described herein. My collaborator at Örebro University, Magnus Grenegård, for a very interesting collaboration, your interest in my polymers and teaching me all I need to know about platelets. My collaborator at Uppsala University, Oommen, for interesting discussions and helpful suggestions. Although some ideas did not make it all the way, we still got a nice paper out of it. My other collaborators in Linköping, Örebro and Uppsala, Chyan-Jang, Queenie, Deepanjali, Caroline, and Knut, for nice collaborations that, luckily, also resulted in papers. VIII Lill-Matte, for all the fruitful discussions over the years. You have an amazing mind for both chemistry and clever "ordvitsar". Keep it up! Rogga, for being one of the best "bollplank" imaginable. I hope we can hit more conferences in the future. Timmy, for introducing me to the world of carbohydrates and giving me invaluable help in the early years. You are one of the best chemists I have ever met. My other colleagues, past and present, at organic chemistry, and Stefan, for your help when I struggled with my syntheses and for all the discussions about chemistry and whatnot. My other colleagues, past and present, at the Chemistry department, and Sara, for your help whenever I needed it and for brightening up my days at the department. Thomas Ederth, for patiently helping me run and interpret the DLS and for putting up with all my questions. Jaywant, for interesting collaborations and ideas. It is a shame we do not have a joint publication yet. My other colleagues past and present in the MolPhys and SurfNano groups, Caroline, Ranjith, Daniel, Abeni, Camilla, Karin, Kajsa, and Erik, for your help to look beyond the borders of organic synthesis and understand the applications. Stefan Klinström and all the other staff and members of Forum Scientium, for helping me keep a wider view of science. Susanne, for patiently guiding me in the jungle of paperwork and forms. The members of the PhD Reference Group, past and present, for all the hard work and dedication over the years. IX The Friday Beer Club (FÖK), Staffan, Robban, Chris, and Skalle-Per, for brightening the end of my weeks.
doi:10.3384/diss.diva-131093 fatcat:yu3v7mbsjrhflnm527b3bd7cpe