3种苯丙胺类药物与溶菌酶的作用机制及构效关系研究  

Study on Reaction Mechanism and Their Structure-Activity Relationship between Three Amphetamines and Lysozyme

作　　者：张爱平[1] 黄茜[1] 郝娟[1] 文雯[1] 高晓亚[1] 

机构地区：[1]山西医科大学药学院,山西太原030001

出　　处：《分析测试学报》2011年第2期140-145,共6页Journal of Instrumental Analysis

基　　金：山西省自然科学基金资助项目(2010011048-1);山西医科大学科技创新基金资助项目(01200806)

摘　　要：在模拟人体生理条件下,采用荧光光谱法研究了3种不同结构的苯丙胺类药物(麻黄碱、伪麻黄碱和甲基麻黄碱)与溶菌酶之间的相互作用,计算了其结合常数、结合位点数和热力学参数,并探讨了3种药物对溶菌酶构象的影响。研究发现,三者可对溶菌酶内源性荧光产生强烈的猝灭作用,其猝灭过程均为静态猝灭。麻黄碱、伪麻黄碱和甲基麻黄碱与溶菌酶均形成1∶1复合物,在308 K温度下的结合常数K分别为5.11×103、4.04×103、2.80×103L.mol-1,结合距离r分别为0.241、0.350、0.422 nm,与溶菌酶结合的焓变分别为-123、-126、-52.1 kJ.mol-1,熵变分别为-329、-339、-103 J.mol-1.K-1。研究结果表明,苯丙胺类药物的构型和取代基对其与溶菌酶的相互作用有重要影响,3种苯丙胺类药物与溶菌酶的作用力顺序为麻黄碱>伪麻黄碱>甲基麻黄碱,体系的主要作用力为氢键和范德华力。溶菌酶与3种药物的同步荧光光谱也表明,溶菌酶的构象在作用前后基本不变。The interactions of lysozyme with ephedrine, pseudoephedrine and methylephedrine, as well as their structure - activity relationship were investigated by fluorescence spectrometry under simulative physiological conditions. The binding constant, the number of binding sites and the thermodynamic parameters were calculated and the effects of ephedrine, pseudoephedrine and methylephedrine on the conformation of lysozyme were studied. The results showed that the endogenous fluorescence of lysozyme was significantly quenched by ephedrine, pseudoephedrine and methylephedrine. The mechanism of fluorescence quenching was static quenching. The 1 ： 1 complex was formed between each amphetamine and lysozyme. The binding constants K of ephedrine, pseudoephedrine and methylephedrine were 5. 11×10^3, 4.04×10^3, 2. 80 ×10^3 · mol^-1 , respectively. According to the theory of Foster dipole - dipole non-radiation energy transfer mechanism, the binding distances r were0.241, 0.350, 0.422 nm, respectively. The enthalpy change（AH）were - 123, - 126, -52. 1 kJ ·mol^-1, the entropy change（△S） were-329, -339, -103 J·mol^-1·K^-1, respectively. The results demonstrated that the configuration and substituted methyl in amphetamines played an important role in the interaction between amphetamines with lysozyme, and the order of the interaction strength between the amphetamines and lysozyme was as follows ： ephedrine 〉 pseudoephedrine 〉 methylephedrine. The hydrogen bond and Vander Waals force were the major driving force between amphetamines and lysozyme. The influences of three amphetamines on the conformation of lysozyme were also investigated with synchronous fluorescence spectra. The result showed that the conformation of lysozyme was not changed by three amphetamines.

关 键 词：麻黄碱 伪麻黄碱 甲基麻黄碱 溶菌酶 荧光光谱法 同步荧光光谱法 

分 类 号：O561.3[理学—原子与分子物理] TQ460.72[理学—物理]