Synthesis, aggregation, and neurotoxicity of the Alzheimer's Abeta1-42 amyloid peptide and its isoaspartyl isomers.
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.
Fukuda
H
H
PE Biosystems Japan Ltd., Tokyo.
Shimizu
T
T
Nakajima
M
M
Mori
H
H
Shirasawa
T
T
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
D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D001224:Aspartic Acid