title: Resolution of localized small molecule-Aβ interactions by deep-ultraviolet resonance Raman spectroscopy.
abstract: The mechanism by which flavonoids prevent formation of amyloid-β (Aβ) fibrils, as well as how they associate with non-fibrillar Aβ is still unclear. Fresh, un-oxidized myricetin exhibited excitation and emission fluorescence maxima at 481 and 531 nm, respectively. Introduction of either Aβ(1-42) or Aβ(25-40) resulted in a fluorescence decrease, when measured at 481 nm, suggesting formation of a myricetin-Aβ complex. Circular dichroism (CD) and ultraviolet resonance Raman (UVRR) studies indicate that the association of myricetin with the Aβ peptide or its hydrophobic fragment, Aβ(25-40), leads to subtle changes in each peptide's conformation. Aβ(25-40) formed amyloid fibrils at a similar rate, when compared to the full-length peptide, Aβ(1-42), using thioflavin T (ThT) fluorescence. Studies also indicated that myricetin was equally effective at preventing the formation of both Aβ(1-42) and Aβ(25-40) fibrils. Although ThT assays indicated that Aβ(1-16) did not form amyloid fibrils, CD studies of the hydrophilic fragment, Aβ(1-16), suggest possible interactions between myricetin and aromatic side chains. UVRR studies of the full-length peptide and Aβ(1-16) showed increases in the intensity of the aromatic modes upon introduction of myricetin. Our findings suggest that myricetin interacts with soluble Aβ via two mechanisms, association with the hydrophobic C-terminal region and interactions with the aromatic side chains.
authors.affiliation: Department of Chemistry, University of Missouri, Columbia, MO 65211, USA.
authors.forename: Mingjuan
authors.initials: M
authors.lastname: Wang
authors.forename: Renee D
authors.initials: RD
authors.lastname: Jiji
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy; D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000378:metabolism*; D052160:Benzothiazoles; D002942:Circular Dichroism; D005419:Flavonoids / Q000494:pharmacology*; D006801:Humans; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D017433:Protein Structure, Secondary; D013059:Spectrum Analysis, Raman / Q000379:methods*; D013844:Thiazoles / Q000737:chemistry
chemical_list: D016229:Amyloid beta-Peptides; D052160:Benzothiazoles; D005419:Flavonoids; D010446:Peptide Fragments; D013844:Thiazoles; C433241:amyloid beta-protein (1-16); C075222:amyloid beta-protein (1-42); C089333:amyloid beta-protein (25-40); C009462:thioflavin T; C040015:myricetin