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

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