Date of Award
Fall 12-2023
Document Type
Thesis
Degree Name
Master of Science (MS)
Department
Pharmaceutical Sciences
First Advisor
Dr. Innokentiy Maslennikov
Second Advisor
Dr. Simin Rahighi
Third Advisor
Dr. Rennolds Ostrom
Abstract
The development of small peptide-based therapeutics can be accelerated by the knowledge of relationships between the peptide structure and its functional interactions. Here, we report the analysis of two groups of synthetic peptides designed for two applications – broad bactericidal action and inhibition of protein-protein interactions in human cells. Novel amphiphilic peptides designed for antibacterial application incorporated arginine as cationic amino acids and non-natural amino acids that have aromatic side chains with similar hydrophobic properties as tryptophan. The interaction of lead cyclic peptides and their linear analogs with a phospholipid bilayer mimicking a bacterial membrane was studied using nuclear magnetic resonance (NMR) spectroscopy. These results provided insight into the mechanism of peptide bactericidal action and the role of the peptide structure in their activity. In the second example, we perform a structural characterization of a peptide designed to modulate the activation of the NF-kappaB signaling pathway. The peptide was designed to mimic the spatial structure of the HOIP-NZF1 domain interacting with the NEMO CC2-LZ domain to suppress the NF-kappaB activation. The structure elucidation of the designed peptide provided vital information about matching the required pharmacophore structure in the peptide.
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.
Recommended Citation
Choi, W. Analyzing Functional Interactions of Designed Peptides by NMR Spectroscopy. [master’s thesis]. Irvine, CA: Chapman University; 2023. https://doi.org/10.36837/chapman.000507
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