Self-assembly and anti-amyloid cytotoxicity activity of amyloid beta peptide derivatives

V. Castelletto, P. Ryumin, R. Cramer, I. W. Hamley*, M. Taylor, D. Allsop, M. Reza, J. Ruokolainen, T. Arnold, D. Hermida-Merino, C. I. Garcia, M. C. Leal, E. Castaño

*Corresponding author for this work

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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 NH 2 -KLVFF-CONH 2 undergoes hydrophobic collapse and amyloid formation at the same critical aggregation concentration (cac). In contrast, NH 2 -K(Boc)LVFF-CONH 2 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 NH 2 -K(Boc)LVFF-CONH 2 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 NH 2 -KLVFF-CONH 2. 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.

Original languageEnglish
Article number43637
Pages (from-to)1-12
JournalScientific Reports
Volume7
DOIs
Publication statusPublished - 8 Mar 2017
MoE publication typeA1 Journal article-refereed

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    Castelletto, V., Ryumin, P., Cramer, R., Hamley, I. W., Taylor, M., Allsop, D., Reza, M., Ruokolainen, J., Arnold, T., Hermida-Merino, D., Garcia, C. I., Leal, M. C., & Castaño, E. (2017). Self-assembly and anti-amyloid cytotoxicity activity of amyloid beta peptide derivatives. Scientific Reports, 7, 1-12. [43637]. https://doi.org/10.1038/srep43637