Enhanced Fibril Fragmentation of N‐Terminally Truncated and Pyroglutamyl‐Modified Aβ Peptides,Angewandte Chemie International Edition

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Enhanced Fibril Fragmentation of N‐Terminally Truncated and Pyroglutamyl‐Modified Aβ Peptides
Angewandte Chemie International Edition ( IF 16.1 ) Pub Date : 2016-03-11 , DOI: 10.1002/anie.201511099
Melanie Wulff ₁ , Monika Baumann ₂ , Anka Thümmler _{3,

4} , Jay K. Yadav ₅ , Liesa Heinrich ₆ , Uwe Knüpfer ₆ , Dagmar Schlenzig ₇ , Angelika Schierhorn ₈ , Jens-Ulrich Rahfeld ₇ , Uwe Horn ₆ , Jochen Balbach ₂ , Hans-Ulrich Demuth ₇ , Marcus Fändrich ₁

Affiliation

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.

中文翻译：

N端截短和焦谷氨酰胺修饰的Aβ肽增强的原纤维断裂

N端截短和焦谷氨酰（pE）的形成是阿尔茨海默氏病中Aβ肽的自然化学修饰。我们在本文中显示这两个修饰显着减少了原纤维长度和原纤维热展开的过渡中点，但是它们基本上不干扰原纤维肽的构象。该观察结果表明，未修饰肽段的N末端可保护Aβ原纤维免受机械应力和断裂作用，并解释了pE修饰肽段形成小且毒性特别大的聚集体的高度倾向。

更新日期：2016-03-11

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