A β-amino acid modified heptapeptide containing a designed recognition element disrupts fibrillization of the amyloid β-peptide

Abstract

We study the complex formation of a peptide βAβAKLVFF, previously developed by our group, with Aβ(1-42) in aqueous solution. Circular dichroism spectroscopy is used to probe the interactions between βAβAKLVFF and Aβ(1-42), and to study the secondary structure of the species in solution. Thioflavin T fluorescence spectroscopy shows that the population of fibers is higher in βAβAKLVFF/Aβ(1-42) mixtures compared to pure Aβ(1-42) solutions. TEM and cryo-TEM demonstrate that co-incubation of βAβAKLVFF with Aβ(1-42) causes the formation of extended dense networks of branched fibrils, very different from the straight fibrils observed for Aβ(1-42) alone. Neurotoxicity assays show that although βAβAKLVFF alters the fibrillization of Aβ(1-42), it does not decrease the neurotoxicity, which suggests that toxic oligomeric Aβ(1-42) species are still present in the βAβAKLVFF/Aβ(1-42) mixtures. Our results show that our designed peptide binds to Aβ(1-42) and changes the amyloid fibril morphology. This is shown to not necessarily translate into reduced toxicity. Copyright © 2010 European Peptide Society and John Wiley & Sons, Ltd.