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

Castelletto, V., Ryumin, P., Cramer, R. ORCID:, Hamley, I. W. ORCID:, Taylor, M., Allsop, D., Reza, M., Ruokolainen, J., Arnold, T., Hermida-Merino, D., Garcia, C. I., Leal, M. C. and Castaño, E. (2017) Self-assembly and anti-amyloid cytotoxicity activity of amyloid beta peptide derivatives. Scientific Reports, 7. 43637. ISSN 2045-2322

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To link to this item DOI: 10.1038/srep43637


The self-assembly of two derivatives of KLVFF, a fragment Abeta(16-20) of the amyloid beta (Abeta) peptide, is investigated and recovery of viability of neuroblastoma cells exposed to Abeta 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 beta-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 beta-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 show their utility, in unaggregated form, in restoring the viability of neuroblastoma cells against Abeta-induced toxicity.

Item Type:Article
Divisions:Interdisciplinary centres and themes > Chemical Analysis Facility (CAF)
ID Code:69512
Publisher:Nature Publishing Group


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