荧光光谱法研究青蒿素类抗疟药与CYP2B6酶的相互作用  

Interactions between Artemisinin or Dihydroartemisinin and CYP2B6 by Fluorescence Spectroscopy

作　　者：孙坤[1] 张爱平[1] 王锐利[1] 李赟[1] 张立伟[2] 张淑秋[1] 

机构地区：[1]山西医科大学药学院,山西太原030001 [2]山西大学分子科学研究所,山西太原030001

出　　处：《分析测试学报》2011年第7期750-754,共5页Journal of Instrumental Analysis

基　　金：国家自然科学基金资助项目(30572367;30973589);山西省回国留学人员科研项目(2009-47);山西医科大学青年基金资助项目(02200704)

摘　　要：在模拟人体生理条件下,采用荧光光谱法及同步荧光法研究了抗疟药青蒿素（ART）和双氢青蒿素（DHA）与药物代谢酶CYP2B6之间的相互作用。结果表明,在温度为296~303 K时,ART和DHA对CYP2B6的猝灭机制均以静态猝灭为主,当温度由303 K升高至310 K时,则为静态猝灭和动态猝灭共同作用的混合猝灭机制;在生理体温310 K时DHA对CYP2B6的结合能力强于ART;当温度范围由296~303 K上升为303~310 K时,ART-CYP2B6体系的主要结合力由氢键和范德华力转变为疏水作用力,而DHA-CYP2B6体系则由静电引力转变为氢键和范德华力,均为自发的热力学反应;同步荧光光谱显示DHA比ART与CYP2B6的结合位点更靠近色氨酸残基,且在室温（298 K）下二者对CYP2B6的构象均影响不大。The binding reactions between antimalarial agent,e.g.artemisinin（ART） or dihydroartemisinin（DHA）,and drug-metabolizing enzyme CYP2B6 were studied by fluorescence quenching spectroscopy at simulated physiological conditions.The structural information of CYP2B6 during their interactions was investigated by synchronous fluorometric method.The results showed that,for both reactions of ART with CYP2B6 and DHA with CYP2B6,the main quenching mechanism was static quenching at temperature range of 296-303 K,and turned to static quenching mixed with dynamic quenching while the temperature increased to 303-310 K.At a physiological temperature of 310 K,the bonding capability of DHA and CYP2B6 was stronger than that of ART and CYP2B6.The main bonding formation of ART to CYP2B6 system was hydrogen bond by Van Der Waals force at the temperature range of 296-303 K,and then changed to hydrophobic force when the temperature stepped up to 303-310 K.However,the main bonding force between DHA and CYP2B6 was electrostatic force at 296-303 K and changed to hydrogen bond by Van Der Waals force when the temperature grew to 303-310 K.All of the reactions were spontaneous thermodynamics reactions.And the synchronous spectra showed that both the bonding sites of ART to CYP2B6 and DHA to CYP2B6 were near to the tryptophane residue of CYP2B6,and the bonding site of DHA was closer than that of ART to the tryptophane residue.Meanwhile,both ART and DHA had little influence on the conformation of CYP2B6 at room temperature（298 K）.

关 键 词：荧光光谱法 同步荧光光谱法 青蒿素 双氢青蒿素 CYP2B6 

分 类 号：O561.3[理学—原子与分子物理] O629.8[理学—物理]