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

ABSTRACT: The self-assembly of two derivatives of KLVFF, a fragment A?(16-20) of the amyloid beta (A?) peptide, is investigated and recovery of viability of neuroblastoma cells exposed to A? (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 ?-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 ?-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 A?-induced toxicity.

SUBMITTER: Castelletto V 

PROVIDER: S-EPMC5341572 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature