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化学学报
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化学学报 ›› 2007, Vol. 65 ›› Issue (24): 2853-2857. 上一篇    下一篇

研究论文

抗肿瘤药物5-氟尿嘧啶与人血清白蛋白相互作用的热力学研究

李林尉*, 王冬冬, 孙德志, 刘敏, 曲秀葵   

  1. (聊城大学化学化工学院 聊城 252059)
  • 投稿日期:2006-10-08 修回日期:2007-04-06 发布日期:2007-12-28
  • 通讯作者: 李林尉

Thermodynamic Study on Interaction between Anti-tumor Drug 5-Fluorouracil and Human Serum Albumin

LI Lin-Wei*; WANG Dong-Dong; SUN De-Zhi; LIU Min; QU Xiu-Kui   

  1. (College of Chemistry and Chemical Engineering, Liaocheng University, Liaocheng 252059)
  • Received:2006-10-08 Revised:2007-04-06 Published:2007-12-28
  • Contact: LI Lin-Wei

PDF

907

被引次数

42

在298.15 K下，根据本结合过程的假设和Langmuir结合理论, 用等温滴定微量热和圆二色谱分析法研究了抗肿瘤药物5-氟尿嘧啶(5-FU)与人血清白蛋白(HSA)的相互作用. 研究结果表明, 蛋白质(HSA)与药物配体5-氟尿嘧啶的相互作用存在两类结合位点. 第一类结合, 结合位点数N＝71±0.1, 结合常数 K＝(1.46±0.016)×105 L•mol－1, 结合焓ΔH＝(39.61±0.220) kJ•mol－1, 结合熵ΔS＝(231.68±0.025) J•mol－1•K－1, 结合自由能ΔG＝(－29.48±0.030) kJ•mol－1. 结合过程为熵驱动过程, 疏水相互作用是过程的主要推动力；第二类结合, 结合位点数N＝140±0.2, 结合常数 K＝(1.49±0.032)×105 L•mol－1, 结合焓ΔH＝(－19.31±0.103) kJ•mol－1, 结合熵ΔS＝(34.30±0.055) J•mol－1•K－1, 结合自由能ΔG＝(－29.53±0.041) kJ•mol－1, 结合过程为焓-熵协同驱动过程, 氢键和静电相互作用是过程的主要推动力. 圆二色谱分析结果表明, 在两类结合过程中, 药物5-氟尿嘧啶(5-FU)的作用致使蛋白质(HSA)二级结构单元的相对含量发生了变化.

关键词: 等温滴定微量热法, 圆二色谱, 5-氟尿嘧啶, 人血清白蛋白

From the assumptions of this binding process and Langmuir’s binding theory, the interaction between 5-fluorouracil and human serum albumin (HSA) has been 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 HSA for the 5-fluorouracil. For the first class of binding, the binding site number is N＝71±0.1, the binding constant is K＝(1.46±0.016)×105 L•mol－1, the binding enthalpy is ΔH＝(39.61±0.220) kJ•mol－1, the binding entropy is ΔS＝(231.68±0.025) J• mol－1•K－1, and the binding Gibbs free energy is ΔG＝(－29.48±0.030) kJ•mol－1. 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 site number is N＝140±0.2, the binding constant is K＝(1.49±0.032)×105 L•mol－1, the binding enthalpy is ΔH＝(－19.31±0.103) kJ•mol－1, the binding entropy is ΔS＝(34.30±0.055) J•mol－1•K－1, and the binding Gibbs free energy is ΔG＝(－29.53±0.041) kJ•mol－1. 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 5-fluorouracil and HSA changed the relative contents of secondary structure units of protein HSA in these two classes of binding processes. The thermodynamic effects of the binding system are integrated results which come from different interactions in the binding process. The conformations of the protein HSA underwent changes induced by the anti-tumor drug 5-fluorouracil in the solution medium of this binding system.

Key words: isothermal titration calorimetry, circular dichroism spectrometry, 5-fluorouracil, human serum albumin