尼洛替尼衍生物与牛血清白蛋白的相互作用  

Interaction between nilotinib derivative and bovine serum albumin

作　　者：李娜[1] 崔柳苏[2] 杨丽娟[1] 王倩倩[1] 刘巍[1] 孙祥德[1] 

机构地区：[1]新乡医学院药学院,河南新乡453003 [2]新乡医学院基础医学院,河南新乡453003

出　　处：《新乡医学院学报》2015年第10期899-902,906,共5页Journal of Xinxiang Medical University

基　　金：河南省教育厅自然科学计划项目(编号:14A150010)

摘　　要：目的探讨尼洛替尼衍生物4-甲氧基-N-[4-(3-吗啉基丙氧基)苯基]-3-[4-(吡啶-3-基)嘧啶-2-基氨基]苯甲酰胺(lz)与牛血清白蛋白(BSA)的相互作用。方法模拟生理条件(p H=7.4),25、37℃测定荧光光谱和吸收光谱。利用Stern-Volmer方程判断荧光猝灭类型;求出结合常数和结合位点数;根据Frster非辐射能量转移理论求出其作用距离r;根据基本热力学参数ΔG、ΔH和ΔS判断lz和BSA作用力类型;根据同步荧光光谱分析lz对BSA构象的影响。结果 lz对BSA的内源荧光有较强的动态猝灭作用,并得出了结合常数(Ka)及结合位点数(n),结合作用主要靠氢键和范德华力驱动,结合距离r=3.20 nm,发生能量转移,引起了BSA构象的变化。结论本研究为进一步改造设计尼洛替尼,寻找新的药物小分子提供了一定的实验依据。Objective To study the interaction between derivative of nilotinib 4-methoxyl-N-[4-（ 3-morpholinopropoxy） phenyl]-3-[4-（ pyridin-3-yl） pyrimidin-2-ylamino] benzamide（ lz） and bovine serum albumin（ BSA）. Methods Physiologicalcondition（ p H = 7. 4）,25 ℃,37 ℃ was simulated to determine the fluorescence and absorption spectra. Fluorescence quenching type was judged by Stern-Volmer equation; the binding constant and number of binding sites was caculated according to binding constant expression. The binding distance between BSA and lz was obtained according to the Frster theory of nonradiation energy; the thermodynamic parameters（ ΔG,ΔH and ΔS） were used to explore the interaction mechanism of lz and BSA,the alteration of conformation of BSA was studied by synchronous fluorescence spectra. Results The quenching of lz to BSA was probably dynamic process,and the binding constant（ Ka） and the number of binding sites（ n） were found,the interaction of lz with BSA was driven mainly by hydrogen bonds and van der Waals force,the distance（ r = 3. 20 nm） was obtained,which indicated that the energy transfer occurred,the conformation of BSA was change. Conclusion This study could provide certain experimental basis for searching new small molecule drugs.

关 键 词：4-甲氧基-N-[4-(3-吗啉基丙氧基)苯基]-3-[4-(吡啶-3-基)嘧啶-2-基氨基]苯甲酰胺 牛血清白蛋白 相互作用 荧光光谱 同步荧光光谱 紫外吸收光谱 

分 类 号：R96[医药卫生—药理学]