贝加因黄酮与不同异构体人血清白蛋白相互作用机制研究  

Interaction between Baicalein and Various Isomers of Human Serum Albumin

作　　者：刘媛[1] 秦川[1] 侯菲儿[1] 谢孟峡[1] 

机构地区：[1]北京师范大学分析测试中心,北京100875

出　　处：《化学学报》2009年第7期629-636,共8页Acta Chimica Sinica

基　　金：北京市新医药学科群(No.XK100270569)资助项目.

摘　　要：贝加因黄酮具有广泛的生理和药理活性,它与蛋白质相互作用机制的研究对于深入了解其药理药效具有重要的意义.采用紫外和荧光光谱等手段对贝加因黄酮与不同异构体的人血清白蛋白复合物的结构进行了表征.在弱碱性条件下,贝加因的紫外吸收光谱发生了明显的变化,说明其A环上的羟基发生了解离,而在pH值4.5～2.0范围内,贝加因的结构基本保持不变.贝加因与不同异构体的人血清白蛋白作用后,其紫外光谱吸收I带发生显著的红移,显示出药物与蛋白质发生了特异性的结合.贝加因对不同异构体的荧光猝灭机制主要为静态猝灭过程,通过药物对蛋白质的荧光猝灭实验,计算了它们之间的结合常数.研究结果表明,药物与蛋白质的结合常数随pH值的降低而减小,这可能与蛋白质的结构变化有关.研究还发现,与不同异构体蛋白质作用后,药物的荧光发射峰有显著的增强效应.上述实验结果充分证明贝加因与不同异构体的蛋白质之间形成了复合物,药物分子结合在蛋白质IIA亚域邻近色氨酸残基的SiteI结合位点.结合计算机分子模拟,对药物与蛋白质的结合模式进行了讨论.Flavonoid baicalein （BAI） has wide biological and pharmacological activities, and investigation on the interaction between BAI and protein plays a key role in understanding its pharmacology. The complexes of BAI with various isomers of human serum albumin （HSA） were characterized by UV absorption and fluorescence spectroscopic approaches. The UV absorption spectra of BAI were significantly changed in weak base condition, signifying that the OH group in the A ring of BAI has been dissociated, while the structure of BAI remained unchanged in the pH range from 4.5 to 2.0. The UV absorption band I of BAI has an obvious red-shift after interaction with various isomers of HSA, indicating that a specific interaction has occurred between BAI and the protein. The fluorescence quenching processes of HSA induced by BAI mainly arose from static quenching, and their binding constants were calculated. The results showed that the binding constants of BAI with HSA decreased with the decrease of the buffer pH values, which probably originated from the changes of the protein structures. The fluorescence emission band of BAI has been significantly enhanced after interaction with different isomers of HSA. From above results, it can be concluded that BAI formed complexes with various isomers of HSA, and the binding site of BAI was located on the sub-domain IIA of HSA, nearing the TRP-214 amino acid residue. Combining the computer molecular modeling, the binding mode between the drug and protein has been discussed.

关 键 词：贝加因 人血清白蛋白 异构体 紫外光谱 荧光光谱 

分 类 号：R285.5[医药卫生—中药学]