牛血清白蛋白聚集体的分解动力学  

Structural insights into bovine serum albumin aggregates by a dissociation kinetic investigation

作　　者：李昊一[1] 李冬敏[1] 马刚[1] 商艳丽[1] 孙英[1] 

机构地区：[1]河北大学化学与环境科学学院药物化学与分子诊断教育部重点实验室,河北保定071002

出　　处：《河北大学学报（自然科学版）》2016年第1期35-42,51,共9页Journal of Hebei University(Natural Science Edition)

基　　金：国家自然科学基金资助项目(21075027);教育部科学技术研究重点项目(211014);高等学校博士学科点专项科研基金联合资助课题(20121301110003);河北省自然科学基金资助项目(B2011201082)

摘　　要：以牛血清白蛋白(BSA)作为模型蛋白,通过浊度法研究BSA形成的无序蛋白聚集体的分解动力学并揭示其复杂结构细节.实验发现,BSA无序聚集体在碱性条件下分解过程有4个动力学阶段,包括1个快速的分解阶段,2个相对较慢的分解阶段和1个动力学惰性阶段.由此推测BSA聚集体中至少含有4种不同的BSA单体形态.Protein aggregation is not only a common problem in biopharmaceutical industry involving protein drugs, but also a devastating phenomenon closely linked to numerous human diseases. Under- standing structural details of protein aggregates is fundamentally important in the prediction and preven- tion of protein aggregation behavior. In this study, we explore to use a turbidity-based dissociation kinetic assay to tackle the complex nature of protein amorphous aggregates by a model protein, bovine serum al- bumin（BSA）. We observe that the dissociation of BSA aggregates under basic condition consists of four distinct kinetic phases, including a burst phase, two relatively slow phases, and one kinetically inert phase. Such kinetic observation allows us to hypothesize that BSA aggregates consist of at least four dif- ferent types of BSA monomeric structures at the molecular level. To the best of our knowledge, this is the first turbidity-based investigation with the aim to elucidate the structural heterogeneity of protein a- morphous aggregates.

关 键 词：蛋白聚集体 牛血清白蛋白 浊度法 动力学 

分 类 号：O643[理学—物理化学]