The p3 peptide, a naturally occurring fragment of the amyloid-β peptide (Aβ) found in Alzheimer's disease, has a greater aggregation propensity in vitro than full-length Aβ, but does not bind Cu2+

被引:6
作者
Ali, F [1 ]
Thompson, AJ [1 ]
Barrow, CJ [1 ]
机构
[1] Univ Melbourne, Sch Chem, Melbourne, Vic 3010, Australia
关键词
alpha-Helix; beta-sheet; circular dichroism; copper binding; electrospray mass spectrometry; peptide synthesis;
D O I
10.1071/CH99169
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
Cerebellar preamyloid from both Down's syndrome and Alzheimer's disease contains the p3 fragment (A beta 17-40/42) as a major amyloid-beta peptide (A beta) component. The p3 peptide was previously shown to form amyloid in vitro, but less readily than full-length A beta. Here we show that the p3 peptide has a greater beta-sheet-forming propensity than full-length A beta. Using circular dichroism spectroscopy we determined that in aqueous solutions the p3 peptide forms beta-sheet structure more readily than full-length A beta. The p3 peptide also has a lower alpha-helical propensity than full-length A beta in the structure-forming solvent trifluoroethanol. These results indicate that the lower amyloidogenicity of the p3 peptide is not related to an inability to form beta-sheet structure. In this study we also show that, unlike full-length A beta, the p3 peptide does not bind Cu2+ ions. This inability to bind copper ions may explain why the p3 peptide appears to play a lesser role in Down's syndrome and Alzheimer's disease related neurodegeneration than does full-length A beta.
引用
收藏
页码:321 / 326
页数:6
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