高等学校化学学报

高等学校化学学报

• 研究论文 • 上一篇    下一篇

抗肿瘤药物替加氟与牛血清白蛋白相互作用的热化学研究

李林尉, 王冬冬, 孙德志, 魏新庭, 刘敏, 赵强   

  1. 聊城大学化学化工学院, 聊城 252059
  • 收稿日期:2007-10-12 修回日期:1900-01-01 出版日期:2008-06-10 发布日期:2008-06-10
  • 通讯作者: 李林尉, 孙德志

Thermochemistry Study on Interaction Between Anti-tumor Drug Tegafur and Bovine Serum Albumin

LI Lin-Wei*, WANG Dong-Dong, SUN De-Zhi, WEI Xin-Ting, LIU Min, ZHAO Qiang   

  1. College of Chemistry and Chemical Engineering, Liaocheng University, Liaocheng 252059, China
  • Received:2007-10-12 Revised:1900-01-01 Online:2008-06-10 Published:2008-06-10
  • Contact: LI Lin-Wei, SUN De-Zhi

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被引次数

14

摘要： 在298.15 K下, 以等温滴定微量热(ITC)实验数据为依据,根据合理假设和Langmuir结合理论, 应用非线性最小方差拟合方法测定了抗肿瘤药物替加氟(Tegafur)与牛血清白蛋白(BSA)结合过程热力学性质的改变. 研究结果表明, 牛血清白蛋白与替加氟相互作用存在两类结合位点: (1) N=52.00±0.12, K=(9.83±0.13)×104 L/mol, ΔH=(30.10±0.17) kJ/mol>0, ΔS=(196.00±0.65) J/(mol·K)>0, ΔG=(-28.50±0.66) kJ/mol<0, 表现为熵驱动过程, 疏水相互作用为过程的主要推动力; (2) N=86.00±0.14, K=(9.35±0.13)×104 L/mol, ΔH=(-19.80±0.17) kJ/mol<0, ΔS=(28.30±0.50) J/(mol·K)>0, ΔG=(-28.40±0.43) kJ/mol<0, 表现为焓-熵协同过程, 氢键和静电相互作用为过程的主要推动力. 圆二色谱(CD)分析结果表明, 抗肿瘤药物替加氟诱导蛋白质(BSA)二级结构单元的相对含量发生了一定程度的变化.

关键词: 替加氟, 牛血清白蛋白, 等温滴定微量热法, 圆二色谱

Abstract: From the assumptions of this binding system and the Langmuir's binding theory, the interaction between tegafur and bovine serum albumin(BSA) was investigated by the nano-watt-scale isothermal titration calorimetry and the circular dichroism(CD) spectrometry at 298.15 K. The results show that there are two classes of binding sites on the protein BSA for tegafur. For the first class of binding, the binding site number is N=52.00±0.12, the binding constant is K=(9.83±0.13)×104 L/mol, the binding enthalpy is ΔH=(30.10±0.17) kJ/mol, the binding entropy is ΔS=(196.00±0.65) J/(mol·K), and the binding Gibbs free energy is ΔG=(-28.50±0.66) kJ/mol. This binding is an entropy driven process, and the hydrophobic interaction is the main motive-force for the process. For the second class of binding, the binding sites number is N=86.00±0.14, the binding constant is K=(9.35±0.13)×104 L/mol, the binding enthalpy is ΔH=(-19.80±0.17) kJ/mol, the binding entropy is ΔS=(28.30±0.50) J/(mol·K), and the binding Gibbs free energy is ΔG=(-28.40±0.43) kJ/mol. This binding is an enthalpy-entropy synergically driven process, and the hydrogen bond and electrostatic interactions are the main motive-force for the process. The analytical results of circular dichroism(CD) spectra show that the interactions between tegafurl and BSA resulted in the change of the relative contents of secondary structure units of protein BSA in these two classes of the binding processes. The thermodynamic effects of the binding system are integrated results which come from different interactional effects in the binding process. The conformations of the protein BSA underwent changes induced by the anti-tumor drug tegafurl in the solution medium of this binding system.

Key words: Tegafur, Bovine serum albumin, Isothermal titration calorimetry, Circular dichroism spectrometry

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