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化学学报
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化学学报 ›› 2007, Vol. 65 ›› Issue (16): 1555-1560. 上一篇    下一篇

研究论文

丹皮酚及其两种同分异构体与牛血清白蛋白相互作用的热力学研究

刘敏1, 朱兰英2, 曲秀葵1, 孙德志*,1, 林瑞森3   

  1. (1聊城大学化学化工学院 聊城 252059)
    (2聊城大学生命科学学院 聊城 252059)
    (3浙江大学化学系 杭州 310027)
  • 投稿日期:2006-11-23 修回日期:2007-04-02 发布日期:2007-08-28
  • 通讯作者: 刘敏

Thermodynamic Study on Interaction of Paeonol and Its Two Isomers with Bovine Serum Albumin

LIU Min1; ZHU Lan-Ying2; QU Xiu-Kui1; SUN De-Zhi*,1; LIN Rui-Sen3   

  1. (1 College of Chemistry and Chemical Engineering, Liaocheng University, Liaocheng 252059)
    (2 College of Life Science and Bioengineering, Liaocheng University, Liaocheng 252059)
    (3 Department of Chemistry, Zhejiang University, Hangzhou 310027)
  • Received:2006-11-23 Revised:2007-04-02 Published:2007-08-28
  • Contact: SUN De-Zhi

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被引次数

37 | 13

在298.15 K下利用等温滴定微量热法研究了丹皮酚(2'-羟基-4'-甲氧基苯乙酮, Pae)及其两种同分异构体(2'-羟 基-5'-甲氧基苯乙酮, Hma; 4'-羟基-3'-甲氧基苯乙酮, Ace)与牛血清白蛋白(BSA)在缓冲溶液(pH≈7.0)中的相互作用. 从药物分子在蛋白质分子上有多种类型相互独立的结合位点的假定出发, 应用Langmuir吸附模型对这三种同分异构体与 BSA 相互作用的量热数据进行了处理. 结果表明, 有两类结合位点存在, 同时计算出了两类结合模式的结合常数、焓变、熵变及吉布斯自由能变等热力学数据. 这两类结合主要以焓驱动为主, 并且在同一类结合位点上, Pae, Hma以及 Ace与BSA结合过程的焓变绝对值依次减小, 这主要是由于客体分子苯环上取代基的相对位置不同而引起热力学数据的差异. 圆二色谱研究表明这三种同分异构体的加入均使BSA的二级结构发生变化, 说明这种生物大分子-药物分子相互作用既包含结合反应也包含小分子诱导BSA分子部分结构改变的过程.

关键词: 等温滴定微量热法, 牛血清白蛋白, 丹皮酚, 圆二色法

Interaction of paeonol (2'-hydroxyl-4'-methoxyacetophenone, Pae) as well as its two isomers (2'-hydroxyl-5'-methoxyacetophenone, Hma and 4'-hydroxyl-3'-methoxyacetophenone, Ace) with bovine serum albumin (BSA) in buffer solutions (pH≈7.0) has been determined with isothermal titration calorimetry at 298.15 K. Data process has been based on the supposition that there are several independent classes of binding sites on each BSA molecule for the molecules of each drug. The results obtained by using this supposition combined with Langmuir adsorption model show that there are two classes of such binding sites. The binding constants, changes of enthalpy, entropy and Gibbs free energy were obtained, which shows that the two classes of binding are mainly enthalpy driven processes. On the same class of binding site, the negative value of binding enthalpy decreased in the order of Pae, Hma and Ace. The difference of thermodynamic data was considered to be caused by the different locations of the substituting groups on aromatic phenyl ring of guest molecules. Circular dichroism (CD) spectra show that the three isomers changed the secondary structure of BSA. These results indicate that such a biomacromolecule-drug interaction includes contributions of the binding and the partial change of structure of BSA molecules induced by the three isomers.

Key words: isothermal titration calorimetry, bovine serum albumin (BSA), paeonol, CD spectra