Prix DuPont des Matériaux 2011 - Apostolovic Bojana
Hybrid Polymer Therapeutics Incorporating Bioresponsive, Coiled Coil Peptide Linkers. Thèse EPFL, no 4770 (2010). Dir.: Harm-Anton Klok.
"Pour le développement de polymères à usage thérapeutique innovants contenant des liens peptides biologiquement actifs".
Hybrid Polymer Therapeutics Incorporating Bioresponsive, Coiled Coil Peptide Linkers.
The term “polymer therapeutics” describes biologically active polymeric drugs, polymer-drug conjugates, polymer-protein conjugates, polymeric micelles to which a drug is covalently bound and multi-component polyplexes (containing covalent linkers) being developed as non-viral vectors for gene and protein delivery.
This Thesis reports the design, synthesis and results of in vitro model studies of a conceptually novel class of polymer therapeutics in which the cargo is attached to a polymer backbone via a non-covalent, biologically-inspired coiled coil linker, which is formed by heterodimerization of two complementary peptide sequences that are linked to the polymer carrier, respectively, the cargo. In contrast to the polymer-drug conjugates prepared so far, in which the drug is typically attached via an enzymatically or hydrolytically cleavable linker, the non-covalent polymer therapeutics proposed in this Thesis offer several potential advantages, including facile access to combination therapeutics and rapid production of compound libraries to screen for structure-activity relationships. Furthermore, the coiled coil based peptide linkers may not only be useful to bind and release guests but may also play an active role in enhancing and directing intracellular transport and trafficking, which may make these constructs of particular interest for the cytosolic delivery of biomolecular therapeutics.