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

Loading...
Thumbnail Image
Journal Title
Journal ISSN
Volume Title
A1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä
Date
2017-03-08
Major/Subject
Mcode
Degree programme
Language
en
Pages
1-12
Series
Scientific Reports, Volume 7
Abstract
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-sheetordering 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.
Description
Keywords
Other note
Citation
Castelletto , V , Ryumin , P , Cramer , R , Hamley , I W , Taylor , M , Allsop , D , Reza , M , Ruokolainen , J , Arnold , T , Hermida-Merino , D , Garcia , C I , Leal , M C & Castaño , E 2017 , ' Self-assembly and anti-amyloid cytotoxicity activity of amyloid beta peptide derivatives ' , Scientific Reports , vol. 7 , 43637 , pp. 1-12 . https://doi.org/10.1038/srep43637