Doctor of Philosophy (PhD)
This work is focused on the design, synthesis and characterization of polypeptide and polypeptoid polymers. The former are composed of amino acid repeat units and possess intramolecular hydrogen bonding interactions allowing for the self-assembly into well-defined secondary structures (e.g. α-helix). Polypeptoids are based on N-alkyl substituted glycine and lack intramolecular hydrogen bonding interactions, resulting in enhanced proteolytic stability and thermal processability. Physicochemical properties of polypeptoids are strongly dependent on the side chain structures, allow for control of the solubility, crystallinity, and conformation of the polymers. Well-defined polypeptides and polypeptoids are synthesized by the ring-opening polymerization (ROP) of their corresponding N-carboxyanhydride monomers (NCA), enabling access to high molecular weight polymers having well-defined structures. Chapter II is focused on the synthesis and characterization of glycopolypeptides by a combination of controlled polymerization methods and copper mediated alkyne/azide cycloaddition chemistry and investigation of the multivalent binding of the glycopolypeptides with Concanavalin A, a model lectin. The focus of the study is on understanding the effect of molecular characteristics of the glycopolypeptides such as chain length, epitope density and backbone conformation on the binding kinetics and stoichiometry. Chapter III is focused on the development of an organo-promoted ring-opening polymerization of N-substituted NCAs using alcohol initiators in conjunction with 1,1,3,3-tetramethylguanidine (TMG), an organic promotor. It was found that TMG activates the alcohols through hydrogen bonding interaction. The activated alcohol moieties can initiate the NCAs polymerizations under mild conditions. It was further revealed that the electronic and steric characteristics of the alcohols impact the initiation efficiency and thus the polymerization behavior. Chapter IV is focused on the synthesis and polymerization of N-thiocarboxyanhydrosulfides (NTA), a mercapto analog of the NCA. NTAs exhibited enhanced moisture-stability but reduced polymerization activities relative to the NCA analogs. Several initiating systems have been uncovered to enable controlled polymerization of NTAs in open air, allowing for access to high molecular weight polypeptides and polypeptoids.
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Chan, Brandon Andrew, "Peptidomimetic Polymers: Advances in Monomer Design and Polymerization Methods" (2016). LSU Doctoral Dissertations. 3676.