Peptide backbone modifications of amyloid β (1-40) impact fibrillation behavior and neuronal toxicity.

ABSTRACT: Fibril formation of amyloid β (Aβ) peptides is one of the key molecular events connected to Alzheimer's disease. The pathway of formation and mechanism of action of Aβ aggregates in biological systems is still object of very active research. To this end, systematic modifications of the Phe₁₉-Leu₃₄ hydrophobic contact, which has been reported in almost all structural studies of Aβ₄₀ fibrils, helps understanding Aβ folding pathways and the underlying free energy landscape of the amyloid formation process. In our approach, a series of Aβ₄₀ peptide variants with two types of backbone modifications, namely incorporation of (i) a methylene or an ethylene spacer group and (ii) a N-methylation at the amide functional group, of the amino acids at position

SUBMITTER: Schwarze B 

PROVIDER: S-EPMC8660793 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature