Structure-Activity Relationships in Heparin Binding and Supramolecular Materials

Multivalent non-covalent interactions between particles can be utilized to direct assembly of the individual components into larger organized structures. This self-assembly process has been widely exploited in the development of novel materials for medicine and nanotechnology. The supramolecular approach was also applied in this thesis to create heparin antidotes and sensors in addition to novel biohybrid materials and halogen bonding -based complexes. In publication I, a library of cationic block copolymers was synthetized to study how the polymer structure affects the electrostatic heparin binding. In short, adjustment of the polymer block lengths altered the binding efficiency, size of the forming complexes and biocompatibility. In publication II, heparin was neutralized with cationic macrocyclic compounds. The compounds were additionally capable of host-guest binding, which enabled colorimetric heparin sensing. Tailoring of the macrocycle structure was shown to be highly important as only the multivalent binders were effective in heparin complexation, and heparin sensing was attained solely with cavity size suitable for the guest binding. Publication III presents a bio-based approach for heparin binding and sensing. Engineered proteins with multiple heparin-binding motifs displayed effective heparin complexation in physiological conditions. Additionally, a fluorescent probe was employed for heparin concentration monitoring. In publication IV, a thermoresponsive polymer with cationic binding motifs was synthetized and combined with apoferritin protein cages to obtain supramolecular complexes. By fine-tuning the assembly conditions, thermoresponsive cocrystals could be produced. Complexes of polymers and resorcinarenes were attained through halogen bonding in publication V. The study revealed that the binding affinity and the assembly morphology of the colloids could be varied by changing the polymer architecture. In conclusion, the studies show that the supramolecular approach involving multivalent weak interactions and tailored molecular design is a competent way to create effective heparin binders and sensors in addition to novel self-assemblies. The information attained from the results can be further used in creation of new materials from polymers, proteins and macrocycles.