荧光光谱法和分子对接研究拉米夫定、依非韦伦、替诺福韦与牛血清白蛋白的相互作用及机制  

Interaction between Bovine Serum Albumin with Lamivudine,Efavirenz,Tenofovir and Its Mechanism by Fluorescence Spectroscopy and Molecular Docking

作　　者：刘荣[1] 

机构地区：[1]上海市公共卫生临床中心药剂科,上海201508

出　　处：《中国药房》2017年第1期49-53,共5页China Pharmacy

基　　金：上海市公共卫生临床中心科研课题计划面上项目(No.2014M07)

摘　　要：目的:研究拉米夫定、依非韦伦、替诺福韦与牛血清白蛋白(BSA)的相互作用及其机制。方法:通过荧光光谱法研究不同温度下不同浓度的拉米夫定、依非韦伦、替诺福韦与BSA的结合反应,分别测定其荧光强度,根据Stern-Volmer方程等公式计算动态猝灭常数(KSV)、表观猝灭常数(Kq)、结合常数(KA)、结合位点(n)和热力学焓变(ΔH)、自由能变(ΔG)、熵变(ΔS),并运用Sybyl6.7 Flex X模块建立这3种药物与BSA的分子对接模型。结果:3种药物与BSA相互作用的Kq均大于2.0×1010L/(mol·s),且随温度的升高而降低,n均接近于1,其热力学函数ΔG<0、ΔS<0、ΔH<0。分子对接模型显示,3种药物主要与BSA的Sudlow部位Ⅰ亚结构域发生结合。结论:3种药物与BSA之间存在相互作用,荧光猝灭方式以静态猝灭为主,结合反应为自发分子作用过程,结合作用力均以氢键和范德华力为主。荧光试验和分子对接研究结果一致,两者可相互补充。OBJECTIVE：To study the interaction between bovine serum albumin（BSA）with lamivudine,efavirenz,tenofovir and its mechanism. METHODS：Fluorescence spectroscopy was used to determine the interaction between BSA with different concentrations of lamivudine,efavirenz,tenofovir under different temperatures. The fluorescence intensity of them were determined respectively;quenching constant（KSV）,apparent quenching constant（Kq）,binding constant（KA）,binding site（n）,thermodynamic enthalpy change（ΔH）,free energy diversification（ΔG）and entropy change（ΔS）were calculated according to Stern-Volmer equation and so on. Molecular docking model of 3 drugs with BSA was established by using Sybyl 6.7 Flex X model. RESULTS：Kqfor the interaction between 3 drugs with BSA were all higher than 2.0×10^10L/（mol·s）,and were decreased with the increase of temperature;all n were close to 1,and thermodynamic functions ΔG〈0,ΔS〈0,ΔH〈0. Molecular docking model showed that 3 drugs were mainly bound with BSA at Sudlow Ⅰ subdomain site. CONCLUSIONS：There are the interaction between 3 drugs with BSA;fluorescence quenching mainly manifests as static quenching;binding reaction belongs to spontaneous molecular action process;binding force mainly includes hydrogen bond and Van der Waals＇ force. The result of fluorescence experiment is consistent with those of molecular docking,and they complement each other.

关 键 词：拉米夫定 依非韦伦 替诺福韦 牛血清白蛋白 荧光光谱法 分子对接 

分 类 号：O657.3[理学—分析化学] R978.7[理学—化学]