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A beta-amino acid modified heptapeptide containing a designed recognition element disrupts fibrillization of the amyloid beta-peptide
Authors:
Valeria
Castelletto
(University of Reading)
,
Ian
Hamley
(Diamond Light Source)
,
Teck
Lim
(University of Oxford)
,
Matias B.
De Tullio
(Fundación Instituto Leloir-Instituto de Investigaciones Bioquímicas de Buenos Aires, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET))
,
Eduardo M.
Castano
(Fundación Instituto Leloir-Instituto de Investigaciones Bioquímicas de Buenos Aires, 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:
January 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: