Racemic mixtures frequently display properties that are different from those associated with their enantiopure counterparts, and are often characterized by higher propensity to form aggregates. Our previous research established that mixing of the enantiomers of Alzheimer amyloid β (Aβ) 42 peptides is an effective strategy to induce an oligomer‐to‐fibril conversion, which puts Aβ42 into a substantially less toxic state. Here, new insights into this chiral inactivation effect are presented. In addition to the commonly used Thioflavin T fibril formation assays, the use of the less aggregation‐prone Aβ40 system allowed us to monitor peptide aggregation by NMR. Whereas enantiopure peptide was well soluble under the chosen experimental conditions and showed no sign of precipitation, addition of one equivalent of the mirror‐image peptide triggered an instant and rapid aggregation, observable through the attenuation of the NMR signal. The racemic Aβ40 fibrils were found by transmission electron microscopy to be distinct in morphology, exhibiting a ~2‐fold narrowing as compared with their enantiopure counterparts.

中文翻译：

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对映体纯和外消旋Aβ40系统差异聚集的新见解

外消旋混合物通常显示出不同于其对映纯对应物的特性，并且通常以形成聚集体的倾向为特征。我们之前的研究表明，将阿尔茨海默氏淀粉样蛋白（Aβ）42肽的对映体混合是诱导寡聚体转化为原纤维的有效策略，从而使Aβ42的毒性大大降低。在这里，介绍了这种手性灭活作用的新见解。除了常用的硫黄素T原纤维形成试验外，还使用了不易聚集的Aβ40系统，这使我们能够通过NMR监测肽的聚集。尽管对映体纯肽在所选的实验条件下可溶，并且没有沉淀迹象，加入一当量的镜像肽可触发瞬间快速聚集，这可通过NMR信号的衰减来观察。通过透射电子显微镜发现外消旋的Aβ40原纤维在形态学上是独特的，与对映体纯对映体相比，展宽了约2倍。