Soluble β-sheet rich oligomers of the peptide β-Amyloid (Aβ) have consistently been shown to exhibit toxicity that leads to a significant amount of the neurodegeneration that occurs in Alzheimer’s Disease (AD) cases. The significance of these oligomeric species to the pathogenicity of this disease is key to the development of therapeutics against it. Unfortunately, elucidating the structures of these oligomers as well as their mechanism of toxicity is difficult due to their heterogeneity and tendency to rapidly interconvert between species. This makes studying and treating AD much more difficult. To combat these limitations, we design macrocyclic β-hairpin peptide mimics of different regions of Aβ and study their structural and physiological properties. This practice allows for the elucidation and synthesis of disease-relevant and stable oligomer mimics of Aβ. Oligomers made in this manner have been used to generate monoclonal antibodies that are currently being used in mouse models of Alzheimer’s Disease to evaluate their therapeutic value. Designing these oligomer models in such a way that maintains as much nativity as possible while enforcing β-hairpin conformation and preventing uncontrolled aggregation requires the use of several chemical tools. Herein we have compared and evaluated the effectiveness of each of these tools in terms of their ability to aid in the study of realistic and manageable Aβ oligomer mimics.

Tools for modeling oligomers of the β-Amyloid peptide

Fall 2022 abstracts, posters, and presentations will launch in mid-September.

ACS Fall 2022

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.