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

蛋白质聚集是由热或氧化应激过程中的部分解折叠和由突变引起的一级结构的改变而促进的。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，蛋白质纯化是进行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、克雅氏病、亨廷顿病和帕金森氏病。本研究以溶菌酶为模型蛋白，研究了胺类化合物对溶菌酶热诱导聚集的抑制作用。此外，我们还研究了添加剂对淀粉样蛋白β和β_2-微球蛋白纤维化的影响，以及小分子胺类化合物对溶菌酶热诱导聚集失活和β_2-微球蛋白纤维化的抑制作用。兹提出以下结论。（1）邻-环己二胺和对苯二胺能阻止溶菌酶的热诱导聚集和失活。在添加剂存在下的溶菌酶的失活速率比在没有添加剂的情况下慢3倍。（ii）对二氨基环己烷和精胺可抑制β_2-微球蛋白的纤维化。在添加剂存在下的原纤维的速率比在不存在添加剂的情况下的原纤维的速率慢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.