Doctor of Philosophy (PhD)
Peptoids are a class of peptidomimetic polymers, which have attracted much attention over the years. Due to their structural similarity to peptides, this group of polymers affords good biocompatibility making them of interest for biomedical applications. This dissertation is largely about the design, synthesis, and characterization of cationic polypeptoids for biological applications, particularly nonviral gene delivery. The dissertation will also cover the development, characterization, and polymerization behavior of a new, air stable N-thiocarboxyanhydride (NTA) monomer.
Introducing functionality, such as small biomolecules and organic compounds can provide distinctive properties to the polymers. Chapter 1 introduces gene therapy and concepts pertinent to the topic. Cell transfection and methods and techniques used to carry out the process are described along with their associated advantages and disadvantages.
Chapter 2 provides an overview on the fundamental aspects of polypeptoids as well as previous and recent developments in synthetic strategies, post-polymerization modification, and biological applications in various fields.
Chapter 3 describes the development of cationic polypeptoids by traditional polymerization and post-functionalization methods. Analogue’s gene delivery capabilities demonstrated in this chapter establish the potential of this peptidomimetic class of polymers as carriers for gene delivery.
Work presented in chapter 4 emphasizes more on the application attribute of cationic polypeptoids via delivery of TNF-a siRNA for effective knockdown of systemic inflammation.
Based upon studies done in chapters 3-4, chapter 5 explores a new direction of varying polymer architectures. The effect of architecture on the nonviral gene delivery of diblock copolypeptoids in serum was assessed.
Research foci of Chapter 6 pertains to the development, characterization, and polymerization of new, N-Allyl N-thiocarboxyanhydrosulfide (NTA), the mercapto analog of the corresponding NCA. The NTA exhibited enhanced moisture-stability but reduced polymerization activities relative to the NCA analogs.
Simpson, Jessica Michelle, "Synthesis, Characterization, and Assessment of Cationic Polypeptoids Toward Gene Delivery and Development of Air Stable N-Substituted N-Thiocarboxyanhydrides" (2018). LSU Doctoral Dissertations. 4521.
Available for download on Saturday, March 23, 2019