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

Journal of Peptide Science : an Official Publication of the European Peptide Society
Valeria CastellettoEduardo M Castaño

Abstract

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

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Citations

Dec 17, 2014·Alzheimer's & Dementia : the Journal of the Alzheimer's Association·Dean HartleyThomas Wisniewski
Jan 31, 2015·Scientific Reports·K RajasekharT Govindaraju

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