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《Angewandte Chemie (Weinheim an der Bergstrasse, Germany)》2017,129(38):11664-11668
Racemates often have lower solubility than enantiopure compounds, and the mixing of enantiomers can enhance the aggregation propensity of peptides. Amyloid beta (Aβ) 42 is an aggregation‐prone peptide that is believed to play a key role in Alzheimer's disease. Soluble Aβ42 aggregation intermediates (oligomers) have emerged as being particularly neurotoxic. We hypothesized that the addition of mirror‐image d ‐Aβ42 should reduce the concentration of toxic oligomers formed from natural l ‐Aβ42. We synthesized l ‐ and D ‐Aβ42 and found their equimolar mixing to lead to accelerated fibril formation. Confocal microscopy with fluorescently labeled analogues of the enantiomers showed their colocalization in racemic fibrils. Owing to the enhanced fibril formation propensity, racemic Aβ42 was less prone to form soluble oligomers. This resulted in the protection of cells from the toxicity of l ‐Aβ42 at concentrations up to 50 μm . The mixing of Aβ42 enantiomers thus accelerates the formation of non‐toxic fibrils. 相似文献
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《Angewandte Chemie (Weinheim an der Bergstrasse, Germany)》2017,129(24):6843-6847
Protein amyloids have received much attention owing to their correlation with serious diseases and to their promising mechanical and optical properties as future materials. Amyloid formation has been conducted by tuning temperature and chemical conditions, so that its nucleation and the following growth are analyzed as ensemble dynamics. A single spherical assembly of amyloid fibrils of cytochrome c domain‐swapped dimer was successfully generated upon laser trapping. The amyloid fibrillar structure was confirmed by fluorescence characterization and electron microscopy. The prepared spheres were further manipulated individually in solution to fabricate a three‐dimensional microstructure and a line pattern. Amyloid formation dynamics and amyloid‐based microstructure fabrication are demonstrated based on direct observation of a single spherical assembly, which foresees a new approach in amyloid studies. 相似文献
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Andreas Müller‐Schiffmann Julia Mrz‐Berberich Aksana Andreyeva Raik Rnicke Dirk Bartnik Oleksandr Brener Janine Kutzsche Anselm H. C. Horn Marco Hellmert Jolanta Polkowska Kurt Gottmann Klaus G. Reymann S. Aileen Funke Luitgart Nagel‐Steger Christine Moriscot Guy Schoehn Heinrich Sticht Dieter Willbold Thomas Schrader Carsten Korth 《Angewandte Chemie (Weinheim an der Bergstrasse, Germany)》2010,122(46):8925-8928
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