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

• Published in: Journal of peptide science 2010-09, Vol.16 (9), p.443-450
• Main Authors: Castelletto, Valeria, Hamley, Ian W, Lim, Teck, De Tullio, Matias B, Castano, Eduardo M
• Format: Article
• Language: English
• ISSN: 1099-1387
• DOI: 10.1002/psc.1271

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