Graduation Year
2023
Document Type
Dissertation
Degree
Ph.D.
Degree Name
Doctor of Philosophy (Ph.D.)
Degree Granting Department
Chemistry
Major Professor
Jianfeng Cai, Ph.D.
Committee Member
Feng Cheng, Ph.D.
Committee Member
Kirpal Bisht, Ph.D.
Committee Member
Wayne Guida, Ph.D.
Keywords
Enzyme-like catalyst, Hydrolysis, Alzheimer’s disease, Aβ inhibition, macrocyclic combinatorial library
Abstract
This dissertation investigates the multifaceted utility of γ-AA peptides in various biological contexts, highlighting their capability in mimicking bioactive proteins, facilitating novel drug discovery, and obstructing protein-protein interactions. Initially, we introduced the design of an ingenious γ-AA peptide scaffold that replicates the hydrolysis capabilities of natural enzymes, with the intention to overcome their stability limitations. Notably, the designed catalyst exhibited excellent esterase activity with the coordination of Zn2+. Subsequently, optimization of a linear γ-AA peptide compound through a dimeric strategy resulted in P3-1, a potent inhibitor of amyloid-β 42. Evidenced by both in vivo and in vitro experiments, its potential for contributing to the early detection and treatment of Alzheimer's Disease was demonstrated. Furthermore, the investigation of cyclic γ-AA peptide library was pursued as an efficient strategy for uncovering bioactive molecules. Two compounds, P4-1, and P4-2, identified from the macrocyclic combinatorial library, displayed a remarkable binding affinity towards Prostaglandin E2 receptor 2, marking a significant stride towards the development of potential therapeutics.
Scholar Commons Citation
Gu, Meng, "Development and application of γ-AA peptide on enzyme mimetic and biomolecular agents" (2023). USF Tampa Graduate Theses and Dissertations.
https://digitalcommons.usf.edu/etd/10781
