title: Modulation of fibril formation by a beta-sheet breaker peptide ligand: an electrochemical approach.
abstract: The development of generic inhibitors in order to control the formation of amyloid fibrils and early oligomers is still an unmet medical need. Here, we demonstrate the applicability of electrochemical analysis for the detection of β-sheet breaker peptide ligands that act as excellent inhibitors of Alzheimer's disease (AD) amyloid-β (Aβ) fibrils and oligomers in vitro. As the case study, a well-defined β-sheet breaker pentapeptide (LPFFD, FibIII) was utilized with Aβ(1-42) peptides. Square wave voltammetry (SWV) measurements were confirmed with simultaneous fluorescence analysis of the same incubated Aβ samples using a well-known fluorescent marker of β-sheet formation, Thioflavin T (ThT). Significant changes in the electrochemical signals were observed for the interaction of the Aβ oligomers with FibIII at the early stages of aggregation. The electrochemical approach, in principle, allowed monitoring β-sheet breaker-Aβ interactions on the time scale of aggregation in a label-free and cost-effective format using screen-printed carbon strip (SPCS) electrodes.
authors.affiliation: Department of Physical and Environmental Sciences, University of Toronto Scarborough, 1265 Military Trail, Toronto, ON, Canada.
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Veloso
authors.forename: Kagan
authors.initials: K
authors.lastname: Kerman
mesh_terms: D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000378:metabolism*; D004563:Electrochemistry / Q000379:methods*; D006801:Humans; D007700:Kinetics; D008024:Ligands; D009842:Oligopeptides / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D010084:Oxidation-Reduction; D010446:Peptide Fragments / Q000737:chemistry* / Q000378:metabolism*; D055503:Protein Multimerization / Q000187:drug effects*; D017433:Protein Structure, Secondary; D013050:Spectrometry, Fluorescence
chemical_list: D016229:Amyloid beta-Peptides; D008024:Ligands; D009842:Oligopeptides; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42)