Amyloid-like assembly is not only associated with pathological events, but also leads to the development of novel nanomaterials with unique properties. Herein, using Fmoc diphenylalanine peptide (Fmoc–F–F) as a minimalistic model, we found that histidine can modulate the assembly behavior of Fmoc–F–F and induce enzyme-like catalysis. Specifically, the presence of histidine rearranges the β structure of Fmoc–F–F to assemble nanofilaments, resulting in the formation of active site to mimic peroxidase-like activity that catalyzes ROS generation. A similar catalytic property is also observed in Aβ assembled filaments, which is correlated with the spatial proximity between intermolecular histidine and F-F. Notably, the assembled Aβ filaments are able to induce cellular ROS elevation and damage neuron cells, providing an insight into the pathological relationship between Aβ aggregation and Alzheimer’s disease. These findings highlight the potential of histidine as a modulator in amyloid-like assembly of peptide nanomaterials exerting enzyme-like catalysis.

淀粉样蛋白的组装不仅与病理事件相关，而且还导致具有独特性质的新型纳米材料的开发。在此，使用Fmoc二苯丙氨酸肽（Fmoc-F-F）作为简约模型，我们发现组氨酸可以调节Fmoc-F-F的组装行为并诱导酶样催化。具体来说，组氨酸的存在会重新排列 Fmoc-F-F 的 β 结构以组装纳米丝，从而形成活性位点以模拟催化 ROS 生成的过氧化物酶样活性。在 Aβ 组装的细丝中也观察到类似的催化特性，这与分子间组氨酸和 FF 之间的空间邻近性相关。值得注意的是，组装的 Aβ 丝能够诱导细胞 ROS 升高并损伤神经元细胞，从而深入了解 Aβ 聚集与阿尔茨海默病之间的病理关系。这些发现强调了组氨酸作为肽纳米材料的淀粉样蛋白样组装中调节剂的潜力，发挥酶样催化作用。