丹参酚酸与牛血清白蛋白结合反应的特性和结构相关性研究  

Characteristic of salvianolic acid binding to bovine serum albumin and structure-performance relationship

作　　者：邹晓丽[1] 王湘敏[1] 郭海方[1] 许卉[1] 刘珂[1] 

机构地区：[1]烟台大学药学院,山东烟台264005

出　　处：《中草药》2010年第8期1271-1274,共4页Chinese Traditional and Herbal Drugs

基　　金：山东省高等学校科技计划项目(J09LF08);山东省高校优秀青年教师国内访问学者项目(2007)

摘　　要：目的研究丹参酚酸与牛血清白蛋白的结合反应特性及其结构相关性。方法运用荧光和紫外光谱法研究了4种小分子天然丹参酚酸类化合物迷迭香酸、紫草酸、丹参酚酸A、丹参酚酸B（SAⅠ~Ⅳ）与牛血清白蛋白（BSA）的相互作用。结果计算得到各SA-BSA结合体系的静态表观结合常数（KA）、结合位点数（n）、能量转移效率（E）、空间距离（r）及热力学常数ΔG、ΔH和ΔS。4种丹参酚酸均能与BSA结合形成非共价复合物,通过静态猝灭和非辐射能量转移共同导致BSA内源荧光的猝灭。结论丹参酚酸A（SAⅢ）主要通过疏水作用力与BSA结合,而其余3种丹参酚酸与BSA的结合则主要由氢键和范德华力驱动。SA-BSA相互作用体系的结合强度可以用综合反应参数[Y=lg（KA×E×n/r）]来表征,其在数值上按SAⅢ→SAⅣ→SAⅡ→SAⅠ的顺序递减,并与分子中所含游离羟基数目和分子体积等结构特性密切相关,可以利用脂-水分配系数（clogP）和单位相对分子质量下的拓扑分子极性表面积（tPSA/Mr）来预测丹参酚酸化合物与蛋白的结合程度。Objective To study the characteristic of salvianolic acid（SA） binding to bovine serum albumin（BSA） and the structure-performance relationship.Methods The interactions between BSA and four natural SA（SAⅠ,rosmaric acid;SAⅡ,lithosperic acid;SAⅢ,salvianolic acid A;and SAⅣ,salvianolic acid B） were investigated by fluorescence and ultraviolet spectroscopy.Results The intrinsic fluorescence of BSA was quenched by SA via forming SA-BSA complexes and non-radiation energy transfer.The parameters of SA-BSA binding process,such as the static apparent association constant KA,the number of binding site n,the efficiency of energy transfer E,the spatial distance r were obtained,and the thermodynamic constants ΔG,ΔH,and ΔS were calculated.Conclusion The results indicate that SAⅢ bounds to BSA mainly through a hydrophobic force and the other three SA-BSA interactions are mainly driven by hydrogen bond and Van der Waals＇ force.Y,a comprehensive binding parameter constructing from the equation Y=lg （KA×E×n/r）,could be used to reflect the interaction extent of SA-BSA system.The Y value changes with the number of free phenolic hydroxyl and molecule volume and decreases in the order of SAⅢ→SAⅣ→SAⅡ→SAⅠ.The results from correlation analysis indicate that it could be possible to estimate SA-BSA binding extent from hydrophobic parameter clogP and topo-polar surface area per unit of molecular weight tPSA/Mr of SA molecule.

关 键 词：丹参酚酸 牛血清白蛋白 相互作用 结构相关性 荧光光谱法 

分 类 号：R286.02[医药卫生—中药学]