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Biological molecules, such as polypeptides, form the basis for most of life's functions. These simple linear polymers made up of only 20 amino acids can fold to form complex and intricate structures that span several length scales. The structures that arise from these molecules stem from their high level of molecular control. Each molecule is an exact sequence with complete monodispersity. From this angstrom level of control, micron scale structures can be assembled. This process is one of the most studied in the history of science, but due to the diversity of amino acids and potential interactions, it is still nearly impossible for scientists to look at a peptide sequence and predict a folded structure. Likewise, it is very difficult to choose a desired structure for a particular function and reverse engineer the linear sequence that will provide that structure. Therefore, there is the need for simplified systems to understand the interactions involved in protein folding and to begin to build the knowledge necessary for engineering similar types of functional structures. This thesis uses sequence specific biomimetic polymers, namely polypeptoids or poly N-substituted glycines, to fundamentally probe the chain conformation and assembly properties of sequence specific polymers. Polypeptoids or N-substituted glycines, are sequence specific biomimetic chains that have the same backbone as polypeptides. However, rather than the side chain being attached through the alpha carbon, it is attached to the backbone nitrogen. This chemical alteration has several implications for the system including the elimination of backbone hydrogen bonding and chirality. This chemical alteration yields a more flexible and tunable chain where intramolecular interactions can be modulated by the introduction of different side chains. In addition, the synthesis of polypeptoids is a simple two step submonomer addition that uses a primary amine as the submonomer. This results in a very high yield synthesis with virtually limitless possibilities for side chains due to the commercial availability of a wide variety of primary amines. Using this modular system, my thesis focuses on understanding the solution self assembly of a sequence specific biomimetic polymer. Much of the work has focused on understanding the single chain conformation and collapse of polypeptoids in order to apply this information to larger self assembly systems. The persistence lengths of several polypeptoids have been measured including those containing secondary structure or ionic groups in order to understand the effect of these factors on the chain conformation. Additionally, the collapse or folding of a single polypeptoid chain into a globule structure is discussed. The impact of monomer sequence on this collapse was investigated and shown to have an important effect both on the coil to globule transition as well as the resulting globule structure. Finally, a hierarchical super helix formed through the assembly of an amphiphilic diblock copolypeptoid is discussed. Using chemical modifications coupled with x-ray scattering, the super structure was shown to include ordering stemming from the angstrom level packing of molecules all the way up to the micron scale diameter of the helix. |
