Self-Assembly and Anti-Amyloid Cytotoxicity Activity of Amyloid beta Peptide Derivatives

Castelletto, V. and Ryumin, P. and Cramer, R. and Hamley, Ian and Taylor, Mark Neville and Allsop, David and Reza, M. and Ruokolainen, J. and Arnold, T. and Hermida-Merino, D. and Garcia, C.I. and Leal, M.C. and Castaño, E. (2017) Self-Assembly and Anti-Amyloid Cytotoxicity Activity of Amyloid beta Peptide Derivatives. Scientific Reports, 7. ISSN 2045-2322

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Abstract

The self-assembly of two derivatives of KLVFF, a fragment Aβ(16–20) of the amyloid beta (Aβ) peptide, is investigated and recovery of viability of neuroblastoma cells exposed to Aβ (1–42) is observed at sub-stoichiometric peptide concentrations. Fluorescence assays show that NH2-KLVFF-CONH2 undergoes hydrophobic collapse and amyloid formation at the same critical aggregation concentration (cac). In contrast, NH2-K(Boc)LVFF-CONH2 undergoes hydrophobic collapse at a low concentration, followed by amyloid formation at a higher cac. These findings are supported by the β-sheet features observed by FTIR. Electrospray ionization mass spectrometry indicates that NH2-K(Boc)LVFF-CONH2 forms a significant population of oligomeric species above the cac. Cryo-TEM, used together with SAXS to determine fibril dimensions, shows that the length and degree of twisting of peptide fibrils seem to be influenced by the net peptide charge. Grazing incidence X-ray scattering from thin peptide films shows features of β-sheet ordering for both peptides, along with evidence for lamellar ordering of NH2-KLVFF-CONH2. This work provides a comprehensive picture of the aggregation properties of these two KLVFF derivatives and shows their utility, in unaggregated form, in restoring the viability of neuroblastoma cells against Aβ-induced toxicity.

Item Type:
Journal Article
Journal or Publication Title:
Scientific Reports
Uncontrolled Keywords:
/dk/atira/pure/subjectarea/asjc/1000
Subjects:
ID Code:
85151
Deposited By:
Deposited On:
09 Mar 2017 09:36
Refereed?:
Yes
Published?:
Published
Last Modified:
26 May 2020 05:39