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

LEAL MC; ARNOLD T; ALLSOP D; CRAMER R; CASTAÑO E; HERMIDA-MERINO D; REZA M; HAMLEY IW; CASTELLETTO V; CASTAÑO E; HERMIDA-MERINO D; REZA M; HAMLEY IW; CASTELLETTO V; GARCIA CI; GARCIA CI; RUOKOLAINEN J; RUOKOLAINEN J; TAYLOR M; TAYLOR M; RYUMIN P; RYUMIN P; LEAL MC; ARNOLD T; ALLSOP D; CRAMER R

SCIENTIFIC REPORTS

NATURE

Año: 2017 vol. 7

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.