The mechanism of the inhibition of protein aggregation that causes conformational diseases by low-moleculer compunds

神经丝氨酸是一种主要在大脑中表达的神经元蛋白，其突变体很容易形成导致痴呆的聚集体。发现了几种抑制神经丝氨酸聚集的化合物，并利用它们成功地获得了人神经丝氨酸的晶体。在2.1Å测定了该化合物的晶体结构，并分析了该化合物与蛋白质的相互作用。此外，这些化合物还能有效地稳定神经丝氨酸的折叠中间体，有望成为治疗药物设计的靶向分子。利用这些化合物对中间体进行了提纯和表征。

Neuroserpin is a neuronal protein predominantly expressed in the brain, and its mutants readily form aggregates that cause dementia. Several compounds that prevent aggregation of neuroserpin were found, and crystals of human neuroserpin were successfully obtained using them. The crystal structure was determined at 2.1Å, and interactions between the protein and the compound were analyzed. Furthermore, the compounds were effective in stabilizing a refolding intermediate of neuroserpin, which is promising for a target molecule in therapeutic drug design. Using the compounds, the intermediate was purified and characterized.