title: Fibrillogenesis of synthetic amyloid-beta peptides is dependent on their initial secondary structure.
abstract: Synthetic peptides containing the sequence of Alzheimer's amyloid-beta peptide (A beta) spontaneously form amyloid-like fibrils in vitro, and have been extensively used to study the factors that modulate fibrillogenesis. Contradictory observations have been reported regarding the neurotoxicity of A beta and the influence of some A beta-binding proteins on in vitro A beta amyloid formation. In this study, we show that A beta 1-40 synthetic peptides obtained from different suppliers, have significantly distinct fibrillogenic properties. No differences were detected in the chemical structure or in the initial assembly state by mass spectroscopy, reverse-phase high performance liquid chromatography and denaturing or non-denaturing gel electrophoresis. However, there was a direct correlation between the ability of soluble peptides to form amyloid and their percentage of beta-sheet structure, as determined by electron microscopy, fluorescence associated to thioflavine T bound to amyloid, and circular dichroism. The data suggest that the determinant factor of A beta fibrillogenesis is the secondary structure adopted by the peptide in its soluble state.
authors.affiliation: Department of Neurology, New York University Medical Center, NY 10016, USA.
authors.forename: C
authors.initials: C
authors.lastname: Soto
authors.forename: E M
authors.initials: EM
authors.lastname: Castaño
authors.forename: R A
authors.initials: RA
authors.lastname: Kumar
authors.forename: R C
authors.initials: RC
authors.lastname: Beavis
authors.forename: B
authors.initials: B
authors.lastname: Frangione
mesh_terms: D000682:Amyloid / Q000737:chemistry / Q000648:ultrastructure; D016229:Amyloid beta-Peptides / Q000138:chemical synthesis / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid; D004586:Electrophoresis; D008854:Microscopy, Electron; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry; D017433:Protein Structure, Secondary; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013997:Time Factors
chemical_list: D000682:Amyloid; D016229:Amyloid beta-Peptides; D010455:Peptides