Synthesis, aggregation, and neurotoxicity of the Alzheimer's Aβ1-42 amyloid peptide and its isoaspartyl isomers

被引：78

作者：

Fukuda, H

Shimizu, T

Nakajima, M

Mori, H

Shirasawa, T

机构：

[1] PE Biosyst Japan Ltd, Minato Ku, Tokyo 1060032, Japan

[2] Tokyo Metropolitan Inst Gerontol, Dept Mol Genet, Itabashi Ku, Tokyo 1730015, Japan

[3] Osaka City Univ, Sch Med, Dept Neurosci, Abeno Ku, Osaka 5458585, Japan

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 1999年 / 9卷 / 07期

关键词：

aggregation; Alzheimer's disease; beta-amyloid peptide; solid phase synthesis;

D O I：

10.1016/S0960-894X(99)00121-3

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Amyloid A beta 1-42 peptide (A beta 1-42) and its isomers with an isoaspartyl residue at position 7 or 23 [A beta 1-42(isoAsp7) and A beta 1-42(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, A beta 1-42(isoAsp23) aggregated more strongly than native A beta 1-42 and showed significant neurotoxicity, while the aggregation ability and neurotoxicity of A beta 1-42(isoAsp7) was weak. This suggests that the isomerization of the aspartyl residues plays an important role in fibril formation in Alzheimer's disease. (C) 1999 Elsevier Science Ltd. All rights reserved.

引用

页码：953 / 956

页数：4