title: Introduction of a fluorescent probe to amyloid-β to reveal kinetic insights into its interactions with copper(II).
abstract: The kinetics of the interactions between amyloid-β (Aβ) and metal ions are crucial to understanding the physiological and pathological roles of Aβ in the normal brain and in Alzheimer's disease. Using the quenching of a fluorescent probe by Cu(2+), the mechanism of Aβ/Cu(2+) interactions in physiologically relevant conditions has been elucidated. Cu(2+) binds to Aβ at a near diffusion-limited rate, initially forming component I. The switching between component I and II occurs on the second timescale, with a significant energy barrier. Component I is much more reactive towards Cu(2+) ligands and likely responsible for initial Aβ dimer formation. Clioquinol (CQ) is shown to sequester Cu(2+) more effectively than other tested ligands. These findings have implications for the potential roles of Aβ in regulating neurotransmission, and for the screening of small molecules targeting Aβ-metal interactions.
authors.affiliation: Institute of Chemical Biology, Imperial College London, London SW7 2AX (UK).
authors.forename: Thomas
authors.initials: T
authors.lastname: Branch
authors.forename: Paul
authors.initials: P
authors.lastname: Girvan
authors.forename: Mauricio
authors.initials: M
authors.lastname: Barahona
authors.forename: Liming
authors.initials: L
authors.lastname: Ying
mesh_terms: D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000378:metabolism; D007464:Clioquinol / Q000737:chemistry; D003300:Copper / Q000737:chemistry*; D004578:Electron Spin Resonance Spectroscopy; D005456:Fluorescent Dyes / Q000737:chemistry*; D007477:Ions / Q000737:chemistry; D007700:Kinetics
chemical_list: D016229:Amyloid beta-Peptides; D005456:Fluorescent Dyes; D007477:Ions; D003300:Copper; D007464:Clioquinol
keywords: amyloid β peptides; copper; fluorescence spectroscopy; kinetics; reaction mechanisms