title: Synthesis, aggregation, and neurotoxicity of the Alzheimer's Abeta1-42 amyloid peptide and its isoaspartyl isomers.
abstract: Amyloid Abeta1-42 peptide (Abeta1-42) and its isomers with an isoaspartyl residue at position 7 or 23 [Abeta1-42(isoAsp7) and Abeta1-42(isoAsp23)] were synthesized in high purity by the Fmoc-solid phase technique, followed by HPLC on a silica-based reversed-phase column under the basic conditions. Importantly, Abeta1-42(isoAsp23) aggregated more strongly than native Abeta1-42 and showed significant neurotoxicity, while the aggregation ability and neurotoxicity of Abeta1-42(isoAsp7) was weak. This suggests that the isomerization of the aspartyl residues plays an important role in fibril formation in Alzheimer's disease.
authors.affiliation: PE Biosystems Japan Ltd., Tokyo.
authors.forename: H
authors.initials: H
authors.lastname: Fukuda
authors.forename: T
authors.initials: T
authors.lastname: Shimizu
authors.forename: M
authors.initials: M
authors.lastname: Nakajima
authors.forename: H
authors.initials: H
authors.lastname: Mori
authors.forename: T
authors.initials: T
authors.lastname: Shirasawa
mesh_terms: D000544:Alzheimer Disease; D016229:Amyloid beta-Peptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D000818:Animals; D001224:Aspartic Acid / Q000737:chemistry*; D002470:Cell Survival / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D007536:Isomerism; D008854:Microscopy, Electron; D009474:Neurons / Q000187:drug effects*; D010446:Peptide Fragments / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D051381:Rats; D017208:Rats, Wistar; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D001224:Aspartic Acid