Thermoresponsive Comb-like Polymers Pendent With Densely Packed Elastin Peptides

Thermoresponsive polypeptides combine the characteristics of stimuli-responsiveness from thermoresponsive polymers and ordered structures frompolypeptides, which have received much attention recently. Elastin-like peptides(ELPs) are one intriguing type of peptides which show thermoresponsive behavior atcertain conditions. Polymers of various architectures carrying ELPs have beenreported, which are bio-compatible and biodegradable, and have shown promisingapplications in drug control release, gene delivery, tissue engineering, proteinpurification and smart interface. However, the main drawback of these reportedpolymer systems are significant: they normally possess thermoresponsive behaviorwith very broad phase transition temperature range.In present thesis, we report for the first time the synthesis of comb-likepolymers which carry two ELP side chains with a sequence of VPGVG. The ELPwas synthesized through solution phase peptide synthesis methodology. By cappingthe peptide chain end with polymerizable unit, comb-like polymers of differentmolar masses were prepared via macromonomer route through free radicalpolymerization. These polymers, together with their deprotected counterparts, werecharacterized. The deprotected polymers show thermoresponsive behavior in buffer,thus their thermoresponsiveness was characterized with UV/Vis spectroscopy, whichreveals deprotected polymers show sharp phase transitions (~3oC) at proper pH.Further analysis show that LCST of deprotected polymers varied with molecularweight, polymer concentration, pH and inorganic salt. Secondary structure analysisof the peptidic polymers indicated that they adopted partially type Ⅱ β-turnconformation.Based on these findings, dynamic covalent chemistry was also applied to thisthermoresponsive system. The chemistry is based on the dynamic covalent Schiff’sbase linkage formed from aldehydes and amino groups. Mixing of deprotected comb-like polymers with amino terminated ELP side chains with oligo(ethyleneglycol)-based dendron G1produced the corresponding dynamic covalent polymers.Their thermoresponsiveness was characterized with UV/Vis spectroscopy. It wasinterestingly found the dynamic linkage was enhanced by heating, whichconsequently reduced the phase transition temperatures. This phenomenon isreversible upon cooling. The LCSTs of dynamic polymers can also be tuned bychange of pH and ratios between the dynamic components.The thermally-induced aggregation processes of the comb-like peptidicpolymers and the corresponding covalent polymers were followed with DLS, andfound particle size from the deprotected polymers were much smaller than theseformed from the dynamic polymers.