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

Abstract : The self-assembly of two derivatives of KLVFF, a fragment A beta(16-20) of the amyloid beta (A beta) peptide, is investigated and recovery of viability of neuroblastoma cells exposed to A beta (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 beta-sheet features obs(e)rved 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-KLVFFCONH2. 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 A beta-induced toxicity
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Submitted on : Wednesday, January 24, 2018 - 1:50:44 PM
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V. Castelletto, P. Ryumin, R. Cramer, I. W. Hamley, M. Taylor, et al.. Self-Assembly and Anti-Amyloid Cytotoxicity Activity of Amyloid beta Peptide Derivatives. Scientific Reports, Nature Publishing Group, 2017, 7, 12 p. ⟨10.1038/srep43637⟩. ⟨hal-01691906⟩



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