Enhanced Fibril Fragmentation of N-Terminally Truncated and Pyroglutamyl-Modified Aβ Peptides.

Enhanced Fibril Fragmentation of N-Terminally Truncated and Pyroglutamyl-Modified Aβ Peptides.
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N 末端截短和焦谷氨酰修饰 Aβ 肽的增强原纤维断裂

DOI:
10.1002/anie.201511099
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发表时间:
2016
期刊:
影响因子:
--
通讯作者:
Fändrich M
Fändrich M
中科院分区:
--
文献类型:
--
作者:
Wulff M;Baumann M;Thümmler A;Yadav JK;Heinrich L;Knüpfer U;Schlenzig D;Schierhorn A;Rahfeld JU;Horn U;Balbach J;Demuth HU;Fändrich M

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N‐terminal truncation and pyroglutamyl (pE) formation are naturally occurring chemical modifications of the Aβ peptide in Alzheimer's disease. We show herein that these two modifications significantly reduce the fibril length and the transition midpoint of thermal unfolding of the fibrils, but they do not substantially perturb the fibrillary peptide conformation. This observation implies that the N terminus of the unmodified peptide protects Aβ fibrils against mechanical stress and fragmentation and explains the high propensity of pE‐modified peptides to form small and particularly toxic aggregates.
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