光谱法和分子模拟研究氨氯地平与牛血清白蛋白的相互作用

摘要

The interaction between amlodipine and bovine serum albumin (BSA) was investigated by a combined spectral and computational approach. The result showed that BSA fluorescence at 342 nm is quenched regularly with the addition of amlodipine, which belongs to the static fluorescence quenching and the binding mechanism is related to the fluorescence resonance energy transfer (FRET). According to Lineweaver - Burk equation, the binding constants between amlodipine and BSAarel.214×104L· mol-1(296 K) and 1.662×l04 L·mol-1(303K), respectively. The calculated thermodynamic parameters( ΔH = 33. 46 kJ·mol-1, AS = 191. 22 J · mol-1·K-1) by Van't Hoff equation showed that hydrophobic interaction plays a major role in the amlodipine - BSA system. The binding of amlodipine and BSA is a spontaneous inter-molecular interaction driven by entropy. Molecular modeling displayed that amlodipine is bound in the large hydrophobic cavity of BSA, which accords well with the result from the spectral experiment.%采用紫外-可见吸收光谱、荧光光谱及分子模拟技术研究了氨氯地平与牛血清白蛋白(BSA)的相互作用.结果发现,氨氯地平对BSA有较强的荧光猝灭作用,其荧光猝灭机制属于静态猝灭；其作用机制属荧光共振能量转移(FRET,Fluorescence Resonance Energy Transfer)；由Lineweaver-Burk方程计算出不同温度下氨氯地平与BSA的亲和常数KA分别为1.214×104 L·mol-1(296K)和1.662 ×104L·mol-1 (303 K)；由Van't Hoff方程计算出△H和△S分别为33.46 kJ·mol-1和191.22 J·mol-1·K-1,二者之间是典型的疏水力相互作用；该过程是一个熵驱动的自发分子间相互作用过程.分子模拟进一步揭示了氨氯地平与BSA的疏水空腔具有较好的相互作用,与光谱实验结果一致.