Phenylalanine Mutation to Cyclohexylalanine Facilitates Triangular Trimer Formation by β-Hairpins Derived from Aβ.

Oligomers of the β-amyloid peptide, Aβ, play a central role in the pathogenesis and progression of Alzheimer's disease. Trimers and higher-order oligomers composed of trimers are thought to be the most neurotoxic Aβ oligomers. To gain insights into the structure and assembly of Aβ oligomers, our laboratory has previously designed and synthesized macrocyclic peptides derived from Aβ and Aβ that fold to form β-hairpins and assemble to form trimers.