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

Sci Rep. 2017 Mar 8:7:43637. doi: 10.1038/srep43637.

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 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Amyloid beta-Peptides / chemistry*
  • Amyloid beta-Peptides / metabolism*
  • Amyloid beta-Peptides / pharmacology
  • Amyloidosis / drug therapy
  • Amyloidosis / metabolism
  • Amyloidosis / pathology
  • Animals
  • Cell Survival / drug effects
  • Molecular Structure
  • Neurons / drug effects
  • Neurons / metabolism
  • Peptide Fragments / chemistry*
  • Peptide Fragments / metabolism*
  • Peptide Fragments / pharmacology
  • Protein Aggregates*
  • Protein Aggregation, Pathological / drug therapy
  • Protein Aggregation, Pathological / metabolism
  • Protein Structure, Secondary
  • Rats
  • Spectrometry, Mass, Electrospray Ionization
  • Spectroscopy, Fourier Transform Infrared
  • X-Ray Diffraction

Substances

  • Amyloid beta-Peptides
  • Peptide Fragments
  • Protein Aggregates
  • amyloid beta-protein (1-40)
  • amyloid beta-protein (16-20)