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

DOI: 10.1038/srep43637 DOI Help

Authors: V. Castelletto (University of Reading) , P. Ryumin (University of Reading) , R. Cramer (University of Reading) , I. W. Hamley (University of Reading) , M. Taylor (Lancaster University) , D. Allsop (Lancaster University) , M. Reza (Aalto University School of Science) , J. Ruokolainen (Aalto University School of Science) , T. Arnold (Diamond Light Source) , D. Hermida-merino (University of Reading) , C. I. Garcia (Consejo Nacional de Investigaciones Científicas y Técnicas) , M. C. Leal (Consejo Nacional de Investigaciones Científicas y Técnicas) , E. Castaño (Consejo Nacional de Investigaciones Científicas y Técnicas)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Scientific Reports , VOL 7

State: Published (Approved)
Published: March 2017
Diamond Proposal Number(s): 13298

Open Access Open Access

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.

Journal Keywords: Neurochemistry; Peptides

Subject Areas: Biology and Bio-materials, Chemistry

Instruments: I07-Surface & interface diffraction

Other Facilities: ESRF