Advancing the field of polypeptoids through the synthesis of novel architectures and thermoresponsive polymers

Abstract

Peptidomimetic polymers are an emerging class of polymers that are structurally related to polypeptides. Due to their structural similarities, these polymers can be used to study some of the physical aspects of polypeptides (for example, protein folding). They are also increasingly being used in the fields of biology and drug-delivery. Some members of peptidomimetic polymers include polyacrylamides, polyoxazolines and polypeptoids. Polymer synthesis and characterization has been performed for both polyacrylamides and polyoxazolines, with research dating back to the 1950s and 1980s respectively. Research in the field of polypeptoids has not been as extensive; however, emerging synthetic strategies are allowing for this class of peptidomimetics to be studied in greater detail and are revealing some interesting aspects of proteins. Current studies involving polypeptoids are expanding the limits of peptidomimetic polymers by developing their potential in materials science. The research presented in this dissertation is aimed at the synthesis of novel polypeptoid based architectures and stimuli responsive polypeptoid systems. The synthesis of macrocyclic brush copolymers using a polypeptoid backbone has been achieved. The method selected for the synthesis this architecture circumvents many of the difficulties associated with prior attempts to make this structure, including high dilution for macrocyclization and linear contaminants in the final product. Typical polymer characterization of this novel architecture suggested that these structures were cyclic and contained poly-ethylene glycol side chains. Polypeptoids that respond to changes in temperature (stimuli responsive polymers) have also been synthesized. The temperature at which the polymer responds can be controlled during the copolymerization of two different monomers. It has also been shown that the architecture of xi the polypeptoid affects the stimuli response of the system. Several different architectures, including linear, cyclic and brush copolymers, are compared and show distinct stimuli responses from one another. The ability to synthesize novel architectures allows for properties to closely studied and eventually exploited. Being a peptidomimetic polymer, polypeptoids have also been shown to biocompatible, making them a possible candidate for a bio-inspired therapeutic system.