离子对人血清白蛋白影响的1HNMR研究  

Effects of Metal Ions on Human Serum Albumin Studied by Radiation Damping Water-Ligand Observed via Gradient Spectroscopy

作　　者：陈瑶[1,2] 孙鹏[1] 刘买利[1] 张许[1] CHEN Yao;SUN Peng;LIU Mai-li;ZHANG Xu(State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, National Center for Magnetic Resonance in Wuhan (Wuhan Institute of Physics and Mathematics, Chinese Academy of Sciences), Wuhan 430071, China;University of Chinese Academy of Sciences,Beijing 100049, China)

机构地区：[1]波谱与原子分子物理国家重点实验室,武汉磁共振中心(中国科学院武汉物理与数学研究所),湖北武汉430071 [2]中国科学院大学,北京100049

出　　处：《波谱学杂志》2017年第3期266-274,共9页Chinese Journal of Magnetic Resonance

基　　金：国家自然科学基金资助项目(21120102038,81227902,20875098,21075132);国家重点基础研究发展计划(“973”计划)资助项目(2013CB910200)

摘　　要：人血清白蛋白(HSA)上有很多的结合位点,对药物及内源性物质的运输有很重要的作用.由于HSA分子量大且结构复杂,核磁共振(NMR)谱图信号重叠严重,因此使用常规的NMR技术很难获得天然丰度HSA上结合位点的信息.我们通过新的谱编辑技术,将横向弛豫加权(T_2W)与RD-Water LOGSY技术相结合(即T2W-RD-Water LOGSY),观察到了天然丰度HSA表面的一些明显的特征信号,且这些信号的分辨率较高;通过pH滴定和2D ~1H-~1H TOCSY实验,我们对观察到的信号做了初步指认,发现部分信号来自于HSA表面的组氨酸;然后,我们通过这些特征信号研究了金属离子与HSA之间的相互作用.结果表明该技术可用于简化天然丰度HSA的谱线,在不对HSA进行突变的情况下,能反映了Zn^(2+)与HSA的强结合作用以及结合位点等信息.Human serum albumin(HSA)contains many metabolite binding sites.It has been widely studied for its functionsin drug transportation.Nuclear magnetic resonance(NMR)is a frequently used tool to study HSA.However,due to its highmolecular weight,the NMR spectra of HSA acquired with the conventional methods are often crowded,making spectralassignment and data interpretation difficult.In this study,a new method,which combined radiation damping water-ligandobserved via gradient spectroscopy(RD-WaterLOGSY)with transverse relaxation weighted(T2W)techniques,wasproposed to simplify the NMR spectra of HSA.With the T2W-RD-WaterLOGSY technique,the effect of pH on HSA wasstudied,as well as the interactions between HSA and Zn2+.The results showed that the relative changes in chemical shiftcould be used as a probe to analyze the pH changes in HSA solution and the interactions between HSA and Zn2+.

关 键 词：核磁共振(NMR) T2W-RD-WaterLOGSY 人血清白蛋白(HSA) Zn2+ 相互作用 

分 类 号：O482.53[理学—固体物理] Q592.1[理学—物理]