中药活性成分土大黄苷与人血清白蛋白的结合反应机制研究  

Binding mechanism of rhaponticin and human serum albumin

作　　者：郭明[1] 徐兴涛[1,2] 吴志武[1] 

机构地区：[1]浙江农林大学化学系,浙江临安311300 [2]塔里木大学生命科学学院,新疆阿拉尔843300

出　　处：《药学学报》2011年第9期1084-1092,共9页Acta Pharmaceutica Sinica

基　　金：国家自然科学基金资助项目(20877072)

摘　　要：应用荧光光谱法结合紫外-可见分光光度法研究了土大黄苷(rhaponticin,RT)与人血清白蛋白(human serum albumin,HSA)的结合反应机制,并考察了金属离子的介导作用。依据不同理论模型测定了反应体系的结合常数K、结合位点数n并进行了分析比较,探讨了荧光猝灭机制。根据Frster非辐射能量转移机制确定了授体-受体间结合距离和能量转移效率。采用同步荧光技术考察了RT对HSA分子构象的影响。结果表明,不同理论模型计算出的结合参数基本相符并显示出RT与HSA的结合反应为形成静态复合物,说明RT在生理条件下能被HSA载运至靶位发挥药效。RT对HSA分子结构域微区构象产生影响,造成亚结构域IIA、IIB的疏水性改变。Co(Ⅱ)、Ni(Ⅱ)的介导作用在RT-HSA反应中起桥联作用并增强RT-HSA的相互作用,即在生理条件下,Co(Ⅱ)、Ni(Ⅱ)对RT药效的发挥起促进作用。The interaction mechanism between rhaponticin（RT） and human serum albumin（HSA） has been studied by fluorescence spectroscopy and absorbance spectra.The mediation effect that the metal ions took part in the interaction has also been discussed in this paper.Based on different theoretical models of fluorescence quenching,the binding constant（K） and binding sites（n） of the interaction were determined and analyzed comparatively.The quenching mechanism of the binding reaction has also been discussed.The binding distance（r） and energy-transfer efficiency（E） between RT/RT-Co（Ⅱ）/RT-Ni（Ⅱ） and HSA were also obtained by virtue of the F rster theory of non-radiation energy transfer.The effect of RT acting on the HSA＇s conformation was analyzed by synchronous fluorescence spectroscopy.The result showed that the result calculated by different theoretical models is generally equivalent and RT bound HSA strongly by forming stable complex,which indicates that HSA under physiological conditions can act as a carrier for RT to be transported to exert effects.The microconformation of HSA changed significantly due to hydrophobicity change in the chemical environment of some fluorescence chromophores in the subdomain IIA and IIB of HSA.Metal ions Co（Ⅱ） and Ni（Ⅱ） can mediate RT-HSA interaction,making the binding of the drug to protein stronger,which indicates that Co（Ⅱ） and Ni（Ⅱ） can enhance rhaponticin＇s medical efficacy under physiological conditions.

关 键 词：土大黄苷 人血清白蛋白 荧光光谱 紫外光谱 介导作用 

分 类 号：O641.3[理学—物理化学]