摘要
在模拟人体生理条件下,利用紫外光谱法、荧光光谱法和同步荧光光谱法结合研究三种羟基蒽醌类药物(1,2-二羟基蒽醌、1,4-二羟基蒽醌和1,8-二羟基蒽醌)与溶菌酶(LYSO)相互作用机制,并探讨其构效关系。紫外结果初步显示,三种羟基蒽醌类药物与LYSO发生相互作用。荧光结果进一步证实三种羟基蒽醌类药物均与LYSO发生结合,且对LYSO的荧光猝灭机制均为静态猝灭并伴随有非辐射能量转移。三种羟基蒽醌类药物与LYSO均存在一个结合位点,它们与LYSO形成1∶1复合物,在303K下,结合常数K分别为8.47×105、4.88×105和5.43×105L·mol-1,结合距离r分别为5.83、5.12和5.14nm,与溶菌酶作用后焓变分别为-41.2、-87.6和-39.0 kJ·mol-1,熵变分别为-22.4、-180和-19.1 J·mol-1·K-1。三种羟基蒽醌类药物与LYSO的作用力均为范德华力和氢键,且作用强弱不同,其顺序为:1,2-二羟基蒽醌>1,8-二羟基蒽醌>1,4-二羟基蒽醌。同步荧光法结果表明三种羟基蒽醌类药物与LYSO相互作用后均导致LYSO构象发生改变。研究结果表明,蒽醌环上羟基位置的不同对羟基蒽醌类药物与溶菌酶结合强弱有较大程度的影响。
The reaction mechanism and structure-acticity relationship of three kinds of hydroxyanthraquinone drugs （ 1, 2-di-hydroxyanthraquinone,1,4-dihydroxyanthraquinone and 1,8-dihydroxyanthraquinone）with lysozyme had been investigated by ultra-violet spectroscopy, fluorescence spectrometry and synchronous fluorescence spectroscopy under simulative physiological condi-tions. Ultraviolet spectroscopy results indicated preliminarily that three kinds of hydroxyanthraquinone drugs interacted with LY-SO. The results of fluorescence spectra further confimed that three kinds of hydroxyanthraquinone drugs interacted with LYSO and the mechanism of fluorescence quenching was static quenching accompanied with non-radiation energy transfer. There was a binding site between LYSO and each hydroxyanthraquinone drug and they formed the 1∶1 compounds. At 303K,the binding constants K of 1,2-dihydroxyanthraquinone,1,4-dihydroxyanthraquinone and 1,8-dihydroxyanthraquinone were 7.52×103,6.44×103and 7.01× 103 L·mol-1 . The binding distances r were 5. 83、5. 12和5. 14nm,respectively. After the interaction between each hydroxyanthra-quinone drug and LYSO,the enthalpy changes were-41. 2,-87. 6 and-39. 0 kJ·mol-1,simultaneously,the entropy changes were-22. 4,-180 and-19. 1 J·mol-1·K-1 ,respectively. The dominant force between three kinds of hydroxyanthraquinone drugs and LYSO was Van der Waals force and hydrogen bond. The sequence of the interaction strength between them was as follows：1, 2-di-hydroxyanthraquinone〉1,8-dihydroxyanthraquinone〉1,4-dihydroxyanthraquinone. The results of synchronous fluorescence spectros-copy showed that three kinds of hydroxyanthraquinone drugs interacted with LYSO induced the changes of the LYSO’ s conforma-tion. The study demonstrated that the different position of hydroxyl group in anthraquinone ring led different binding capacity be-tween each hydroxyanthraquinone drug and LYSO.
出处
《化学研究与应用》
CAS
CSCD
北大核心
2014年第5期679-684,共6页
Chemical Research and Application
基金
山西省自然科学基金项目(2010011048-1)资助
山西医科大学科技创新基金项目(01200806)资助
关键词
溶菌酶
1
4-二羟基蒽醌
光谱法
构效关系
lysozyme
1,2-dihydroxyanthraquinone
1,4-dihydroxyanthraquinone
1,8-dihydroxyanthraquinone
spectroscopic meth-odology
structure-acticity relationship
