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

DOI: 10.1002/psc.1271 DOI Help

Authors: Valeria Castelletto (University of Reading) , Ian W. Hamley (The University of Reading; Diamond Light Source) , Teck Lim (University of Oxford) , Matias B. De Tullio (Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET)) , Eduardo M. Castano (Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET))
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Journal Of Peptide Science , VOL 16 (9) , PAGES 443-450

State: Published (Approved)
Published: July 2010

Abstract: 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.

Journal Keywords: Amyloid Beta Peptide; Beta-Amino Acid Peptide; Amyloid; Fibril

Subject Areas: Biology and Bio-materials, Chemistry

Technical Areas:

Added On: 23/09/2010 10:52

Discipline Tags:

Non-Communicable Diseases Health & Wellbeing Biochemistry Chemistry Life Sciences & Biotech

Technical Tags: