title: Self-Assembly and Anti-Amyloid Cytotoxicity Activity of Amyloid beta Peptide Derivatives.
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-CONH2undergoes hydrophobic collapse and amyloid formation at the same critical aggregation concentration (cac). In contrast, NH2-K(Boc)LVFF-CONH2undergoes 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-CONH2forms 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.
authors.affiliation: School of Chemistry, Pharmacy and Food Biosciences, University of Reading, Whiteknights, Reading RG6 6AD, UK.
authors.forename: V
authors.initials: V
authors.lastname: Castelletto
authors.affiliation: School of Chemistry, Pharmacy and Food Biosciences, University of Reading, Whiteknights, Reading RG6 6AD, UK.
authors.forename: P
authors.initials: P
authors.lastname: Ryumin
authors.affiliation: School of Chemistry, Pharmacy and Food Biosciences, University of Reading, Whiteknights, Reading RG6 6AD, UK.
authors.forename: R
authors.initials: R
authors.lastname: Cramer
authors.affiliation: School of Chemistry, Pharmacy and Food Biosciences, University of Reading, Whiteknights, Reading RG6 6AD, UK.
authors.forename: I W
authors.initials: IW
authors.lastname: Hamley
authors.affiliation: Division of Biomedical and Life Sciences, Faculty of Health and Medicine, Lancaster University, Lancaster LA1 4YQ, UK.
authors.forename: M
authors.initials: M
authors.lastname: Taylor
authors.affiliation: Division of Biomedical and Life Sciences, Faculty of Health and Medicine, Lancaster University, Lancaster LA1 4YQ, UK.
authors.forename: D
authors.initials: D
authors.lastname: Allsop
authors.affiliation: Department of Applied Physics, Aalto University School of Science, Aalto FI-00076, Finland.
authors.forename: M
authors.initials: M
authors.lastname: Reza
authors.affiliation: Department of Applied Physics, Aalto University School of Science, Aalto FI-00076, Finland.
authors.forename: J
authors.initials: J
authors.lastname: Ruokolainen
authors.affiliation: Diamond Light Source Ltd., Harwell Science and Innovation Campus, Didcot OX11 0DE, UK.
authors.forename: T
authors.initials: T
authors.lastname: Arnold
authors.affiliation: European Synchrotron Radiation Facility, ESRF, 71 avenue des Martyrs, 38000 Grenoble, France.
authors.forename: D
authors.initials: D
authors.lastname: Hermida-Merino
authors.affiliation: Fundación Instituto Leloir and Instituto de Investigaciones Bioquímicas de Buenos Aires, Consejo Nacional de Investigaciones Científicas y Técnicas, Buenos Aires, Argentina.
authors.forename: C I
authors.initials: CI
authors.lastname: Garcia
authors.affiliation: Fundación Instituto Leloir and Instituto de Investigaciones Bioquímicas de Buenos Aires, Consejo Nacional de Investigaciones Científicas y Técnicas, Buenos Aires, Argentina.
authors.forename: M C
authors.initials: MC
authors.lastname: Leal
authors.affiliation: Fundación Instituto Leloir and Instituto de Investigaciones Bioquímicas de Buenos Aires, Consejo Nacional de Investigaciones Científicas y Técnicas, Buenos Aires, Argentina.
authors.forename: E
authors.initials: E
authors.lastname: Castaño
mesh_terms: D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000378:metabolism* / Q000494:pharmacology; D000686:Amyloidosis / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D015394:Molecular Structure; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D010446:Peptide Fragments / Q000737:chemistry* / Q000378:metabolism* / Q000494:pharmacology; D066329:Protein Aggregates; D066263:Protein Aggregation, Pathological / Q000188:drug therapy / Q000378:metabolism; D017433:Protein Structure, Secondary; D051381:Rats; D021241:Spectrometry, Mass, Electrospray Ionization; D017550:Spectroscopy, Fourier Transform Infrared; D014961:X-Ray Diffraction
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; D066329:Protein Aggregates; C078592:amyloid beta-protein (1-40); C529399:amyloid beta-protein (16-20)