Liu Jiaqin, Tian Jianniao, Tian Xuan, Hu Zhide, Chen Xingguo
Department of Chemistry, Lanzhou University, Lanzhou 730000, China.
Bioorg Med Chem. 2004 Jan 15;12(2):469-74. doi: 10.1016/j.bmc.2003.10.030.
This study was designed to examine the interaction of isofraxidin with human serum albumin (HSA) under physiological conditions with drug concentrations in the range of 3.3 x 10(-6) mol L(-1)-3.0x10(-5) mol L(-1) and HSA concentration at 1.5 x 10(-6) mol L(-1). Fluorescence quenching methods in combination with Fourier transform infrared (FT-IR) spectroscopy and circular dichroism (CD) spectroscopy were used to determine the drug-binding mode, the binding constant and the protein structure changes in the presence of isofraxidin in aqueous solution. Spectroscopic evidence showed that the interaction results in one type of isofraxidin-HSA complex with binding constants of 4.1266 x 10(5) L mol(-1), 3.8612 x 10(5) L mol(-1), 3.5063 x 10(5) L mol(-1), 3.1241 x 10(5) L mol(-1) at 296 K, 303 K, 310 K, 318 K, respectively. The thermodynamic parameters, enthalpy change (DeltaH) and entropy change (DeltaS) were calculated to be -10.08 kJ mol(-1) and 73.57 J mol(-1) K(-1) according to van't Hoff equation, which indicated that hydrophobic interaction played a main role in the binding of isofraxidin to HSA. The experiment results are nearly in accordance with the calculation results obtained by Silicon Graphics Ocatane2 workstation.
本研究旨在考察在生理条件下，异秦皮啶与人类血清白蛋白（HSA）在药物浓度范围为3.3×10⁻⁶ mol L⁻¹ - 3.0×10⁻⁵ mol L⁻¹且HSA浓度为1.5×10⁻⁶ mol L⁻¹时的相互作用。采用荧光猝灭法结合傅里叶变换红外（FT - IR）光谱和圆二色（CD）光谱来确定药物结合模式、结合常数以及在水溶液中存在异秦皮啶时蛋白质结构的变化。光谱证据表明，这种相互作用产生了一种异秦皮啶 - HSA复合物，在296 K、303 K、310 K、318 K时的结合常数分别为4.1266×10⁵ L mol⁻¹、3.8612×10⁵ L mol⁻¹、3.5063×10⁵ L mol⁻¹、3.1241×10⁵ L mol⁻¹。根据范特霍夫方程计算得到的热力学参数，焓变（ΔH）和熵变（ΔS）分别为 - 10.08 kJ mol⁻¹和73.57 J mol⁻¹ K⁻¹，这表明疏水相互作用在异秦皮啶与HSA的结合中起主要作用。实验结果与Silicon Graphics Ocatane2工作站获得的计算结果几乎一致。
