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化学学报
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化学学报 ›› 2008, Vol. 66 ›› Issue (21): 2365-2370. 上一篇    下一篇

研究论文

光谱法与分子模拟研究胡椒碱对牛血清白蛋白的键和作用

何文英*,a 陈光英b 杜 娟c 姚晓军c

  

  1. (a海南师范大学化学系 海口 571158)
    (b海南省热带药用植物化学重点实验室 海口 571158)
    (c兰州大学化学化工学院 兰州 730000)

  • 投稿日期:2008-04-21 修回日期:2008-05-21 发布日期:2008-11-14
  • 通讯作者: 何文英

Investigation on the Binding of Piperine to Bovine Serum Albumin by Optical Spectroscopy and Molecular Modeling

HE, Wen-Ying *,a CHEN, Guang-Ying b DU, Juan c YAO, Xiao-Jun c

  

  1. (a Department of Chemistry, Hainan Normal University, Haikou 571158)
    (b Hainan Provincal Key Laboratory of Tropical Pharmaceutical Herb Chemistry, Haikou 571158)
    (c Department of Chemistry, Lanzhou University, Lanzhou 730000)
  • Received:2008-04-21 Revised:2008-05-21 Published:2008-11-14

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利用荧光光谱法及紫外吸收光谱法结合计算机模拟技术研究了在模拟生理条件下胡椒碱(piperine)与牛血清白蛋白(Bovine Serum Albumin, BSA)的相互作用. 根据荧光猝灭的有关方程分别求得不同温度下(298, 308和318 K)药物与蛋白相互作用的结合常数、结合位点数及键合距离. 实验所得到的热力学参数(ΔHӨ＝－9.55 kJ/mol, ΔSӨ＝46.75 J•mol－1•K－1)表明维持药物与蛋白质的相互作用力主要是疏水作用和静电作用. 分子模拟的结果显示了胡椒碱与BSA的键合机理和键合模式, 表明维持药物与蛋白质的相互作用力主要是疏水作用和氢键(位于氨基酸残基His 242, Arg 222和Arg 218位). 此外, 基于胡椒碱的荧光猝灭效应, 首次探讨了药物-蛋白质体系的几种物理化学参数, 包括电荷密度(δ)、离解常数(Kd)及量子产率(F)的变化效应.

关键词: 胡椒碱, 牛血清白蛋白, 相互作用, 荧光光谱, 分子模拟

The interaction of piperine with bovine serum albumin (BSA) was investigated by fluorescence and absorption spectra in combination with molecular modeling under the simulated physiological conditions. The binding constants and the number of binding sites between piperine and BSA at different temperatures (298, 308 and 318 K) were calculated according to the data obtained from fluorescence titration. The results of spectroscopic measurements and the thermodynamic parameters obtained (the enthalpy change ΔHӨ and the entropy change ΔSӨ were calculated to be －9.55 kJ•mol－1 and 46.75 J•mol－1•K－1 according to the Van’t Hoff equation) suggested that hydrophobic and electrostatic interaction be the predominant intermolecular forces stabilizing the complex. Molecular docking was performed to reveal the possible binding mode or mechanism, suggesting that piperine can strongly bind to BSA. Under the conditions studied, the values of the negative charge density (δ), the dissociation constants (Kd) and quantum yield (F) of piperine-BSA system were calculated.

Key words: piperine, bovine serum albumin (BSA), interaction, fluorescence spectroscopy, molecular modeling