差示扫描微量热法研究蛋白质及其相关体系进展  

Recent progress in protein and protein-related systems using DSC techniques

作　　者：孙海源 邓耿[1] 周瑜[1] 尉志武[1] SUN HaiYuan DENG Geng ZHOU Yu YU ZhiWu(Key Laboratory of Bioorganic Phosphorous Chemistry and Chemical Biology, Ministry of Education, Department of Chemistry, Tsinghua University, Beijing 100084, China)

机构地区：[1]清华大学化学系,生命有机磷化学及化学生物学教育部重点实验室,北京100084

出　　处：《科学通报》2016年第28期3091-3099,共9页Chinese Science Bulletin

基　　金：国家自然科学基金(21273130)资助

摘　　要：蛋白质是一类重要的生物大分子,其结构与性质得到了广泛的研究.差示扫描微量热法(DSC)可以获得蛋白质的热容(C_p)与温度的关系,对我们认识蛋白质的性质有重要的帮助作用.同时,DSC研究蛋白质相关体系新方法也在不断涌现.本文介绍了差示扫描微量热法在研究蛋白质解折叠机理、蛋白质稳定性以及复杂蛋白质体系等几个方面的进展.As one family of the most important biomoleclues, proteins have gained more and more attention since the day they were discovered and the trend is still growing. Even so, many problems are emerging in this filed and thus new techiniques and ideas are required for solving these problems. In this regard, differential scanning calorimetry（DSC） is a conventional but useful method to obtain the relationship between heat capacity and temperature of peoteins. In the past decade, new ideas have been applied to DSC and new methods have been developed. This is reflected in this minireview. First, important progresses have been made on protein unfloding or folding mechanisms. A new method called ＂interruption-incubation protocol＂ was developd to judge wheather a protein unfolds in a two-state mechanism or not. Compared to the conventional van＇t Hoff analysis method, the new approach breaks the limitations of old method on the requirement of protein properties, namely the reversibility of protein folding and the equilibrium assumption during the unfoding process. Also, this method avoids the inaccuracies of enthalpy change for protein unfolding caused by improper baseline determination. Thus, the ＂interruption-incubation protocol＂ has a lower possibility of misjudgement and turns out to be an effective way for analysing ＂two-state or non-two state＂ proteins. In addition, by combining DSC with phase transition models instead of chemical equilibrium assumption, several theories were proposed which can provide a rough landscape of protein folding or unfolding process. Among these theories, the ＂variable barrier model＂ is an interesting one, which can directly give the barrier heights in protein folding as long as the barrier heights are smaller than ~4RT. Second, a new method was proposed to derive protein stability curve directly by combining DSC with isothermal chemical denaturation（ICD） method. This method targets those ＂problematic＂ proteins, when the denaturation process is not perfect reversi

关 键 词：差示扫描微量热 蛋白质 解折叠 蛋白质稳定性 淀粉样纤维 疾病诊断 

分 类 号：O629.73[理学—有机化学]