Date of Award
Master of Science in Chemical Sciences (MSCB)
Thomas C. Leeper
Carol A. Chrestensen
Christopher R. Dockery
Protein therapeutics hold high efficacy in treatment for various diseases including cancer and diabetes. However, the treatment cost is generally higher than other therapeutics mainly due to in vivo protein degradation. This drawback creates demand for more efficient delivery methods to preserve the function and integrity of protein therapeutics. Thermoresponsive coacervate-forming biodegradable polyesters (TR-PEs) are a thermoresponsive molecular packaging system used in protein therapeutic research. The term coacervate refers to a phase-separated solution in which a dense polymer phase separates from the aqueous phase to form nanodroplets within solution, capturing bioactive molecules. Limited research demonstrates if TR-PEs can encapsulate and preserve a larger protein’s activity and how these TR-PEs interact with a protein on the biophysical level. It was determined that TR-PEs encapsulated and released active β-galactosidase enzyme. Encapsulation was visualized using confocal fluorescence microscopy and by labeling β-galactosidase with fluorescein isothiocyanate. Interactions between 15N-isotopically labelled human ubiquitin c and TR-PEs were investigated through variable temperature nuclear magnetic resonance. It was interpreted that TR-PEs non-specifically interact with 15N-ubiquitin and that various pendant groups within a given polymer resulted in non-significant differences. Although TR-PEs may not be specifically interacting with the model cargos, demonstrating that TR-PEs capture and release an unaltered, complex protein exemplifies the viability of using TR-PEs for future therapeutic packaging and possible delivery.
Casterline, Conner, "Analyzing the interactions of thermoresponsive coacervate-forming biodegradable polyester encapsulation on model protein structure and activity" (2022). Master of Science in Chemical Sciences Theses. 51.
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