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

Research output: Contribution to journalArticleScientificpeer-review

40 Citations (Scopus)
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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
Publication statusPublished - 8 Mar 2017
MoE publication typeA1 Journal article-refereed


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