Content area
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 amyloidβ 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.
