Thermoresponsive Collagen Mimetic Polypeptides

Collagens are the most abundant proteins in human body, which have typical triple helix conformations and various hierarchical self-assembly morphologies. Based on their excellent bio-compatibility, collagens are widly used in biomedical materials. On the other hand, oligo(ethylene glycol)s(OEGs) are well-known biocompatible moieties which can not only enhance the solubilization but also mediate thermoresponsiveness to polymers. Furthermore, based on the amphiphilicity, OEGs show shielding effect on polymer. In present thesis, a group of OEGylated collagen mimetic polypeptides were synthesized effciently, and their thermoresponsiveness, secondary comformation and self-assembly behaviors investigated. The details are described as follows:1. The systhesis of OEGylated collagen mimetic polypeptides(CMPs). OEGs moieties were first linked to peptides by etherification through KOH-DMSO methodology. Then three types of OEGylated CMPs carrying either linear OEG(PDEG) and methoxyl(PMe) or ethoxyl(PEt) dendritic OEG pendants were prepared via polycondensation of active ester from the corresponding OEGylated tripeptide precursors. High molar mass CMPs were achieved by adding coupling reagents after polymerization of the macromonomers for certain time. The molar mass, molecular structure and hydrodynamic radius of CMPs were analyzed by GPC, NMR, IR and DLS measurements.2. Thermoresponsiveness and secondary strcture of OEGylated CMPs. Not only the molecular structure and molar mass, but also the heat history and aggreagation states showed remarkable influence on thermoresponsive behaviors of CMPs. On the other hand, the OEGylated CMPs showed enhanced triple helix stability, however the thermal induced phase transition behaviors may perturb the CMPs conformations. The influence of OEGylation on both the themoreponsive behaviors and secondary structures of CMPs were examined to understand the possible shielding effects of OEG dendrons.3. The self-assembly properties of OEGylated CMPs. OEGylated CMPs showed enhanced self-assembly both in bulk and solutions. We first report on the self-assemly of different CMPs in aqueous solution at different temperature. Then we studied the self-assembly of CMPs in organic solutions. Molecular structure, molar mass, solvent polarity, substrate, concentration and temperature showed influence on self-assembly morphologies. At last, solvent induced crystallization was achieved for the OEG dendronized CMPs, in which temperature and aggregation states were important factors. This was the first work to achieve self-assembly of OEGylated CMPs by radial amphiphilicity.