Studies about protein structural alteration switching using in vivo mimic system.

蛋白质聚集是由热应激或氧化应激时的部分展开和突变引起的初级结构改变所促进的。蛋白质聚集是生物医学和生物技术领域的一个主要问题。此外，随着基因组数据的不断扩大，蛋白质纯化是开展后基因组研究的关键之一。在我们的活细胞中，蛋白质聚集体与致命疾病高度相关，如阿尔茨海默氏症、克雅氏症、亨廷顿氏症和帕金森病。在本研究中，我们重点研究了胺类化合物作为添加剂来防止溶菌酶的热诱导聚集，作为一种模式蛋白质。此外，我们还研究了添加剂存在下β淀粉样蛋白和β_2微球蛋白的纤维形成。我们研究了小胺类化合物是否能阻止热诱导的溶菌酶聚集和失活以及β_2微球蛋白的纤化。本文提出以下结论：(i)o-二氨基环己烷和对苯二胺阻止热诱导的溶菌酶聚集和失活。有添加剂时溶菌酶的失活速率比无添加剂时慢3倍。（ii）对二氨基环己烷和精胺阻止β_2微球蛋白的纤化。添加添加剂时原纤维的速率比不添加添加剂时慢4倍。这些数据为防止蛋白质聚集的小添加剂提供了新的候选物。

Protein aggregation is facilitated by a partial unfolding during thermal or oxidative stress and byalterations in primary structure caused by mutation. Protein aggregation is a major problem in biomedical and biotechnological fields. In addition, with a growing expansion of genomic data, protein purification is one of the keys to perform post-genomic researches. In our living cells, protein aggregates are highly associated with fatal diseases, such as Alzheimer's, Creutzfeldt-Jakob, Huntington's and Parkinson's diseases. In this research, we focus on amine compounds as additive for preventing heat-induced aggregation of lysozyme, as a model protein. Furthermore, we investigated the fibrillogenesis of amyloid β and β_2-microglobulin in the presence of the additives.We investigated whether small amine compounds prevent heat-induced aggregation and inactivation of lysozyme and fibrilization of β_2-microglobulin. The following conclusions are proposed.(i)o-Diaminocyclohexane and p-phenylenediamine prevented heat-induced aggregation andinactivation of lysozyme. The inactivation rates of lysozyme in the presence of the additives were 3-fold slower than that in the absence of additives. (ii)p-Diaminocyclohexane and spermine prevented fibrilization of β_2-microglobulin. The rate of the fibrils in the presence of the additives is 4-fold slower than that in the absence of additives. These data provided new candidates for small additives to prevent protein aggregation.