霉酚酸钠和吗替麦考酚酯与人血清蛋白相互作用机制的比较研究

Comparative Study on the Interaction Mechanism of Mycophenolate Sodium and Mycophenolate Mofetil with Human Serum Albumin

利用荧光光谱法和分子对接比较研究了新型免疫抑制剂霉酚酸的两个前药吗替麦考酚酯和霉酚酸钠与人血清蛋白(HSA)相互作用。结果表明,两种药物与HSA之间以1∶1结合形成复合物,猝灭机制均为静态猝灭。不同温度下荧光猝灭实验计算了结合参数,结果显示两种药物对HSA均有猝灭,且霉酚酸钠猝灭更为显著。三维和同步荧光结果表明两个药物单体的加入均对HSA的构象产生了影响。分子对接结果显示配体和蛋白间有氢键生成,结合热力学结果说明药物与HSA之间的相互作用力主要是氢键和范德华力,且霉酚酸钠的结合能力更强。综上结果表明霉酚酸钠能更好的结合HSA,从而在体内运转和代谢的更快。相关研究工作不仅从分子层面阐明了两种药物单体与蛋白的结合机制,而且可为免疫抑制剂类药物的临床用药选择提供一定的理论依据。

The study evaluated the interaction between mycophenolate mofetil(MMF) and sodium mycophenolate(MPS) with human serum albumin(HSA) using fluorescence spectrometry and docking simulation.Results revealed that complexes were formed between MMF/MPS and HSA,and the quenching mechanism was static quenching.The binding parameters calculated at different temperatures showed MPS had stronger capability than MMF to quench the fluorescence of HSA.Furthermore, three-dimensional and simultaneous fluorescence spectra indicated that the conformation of HSA was changed with the addition of drug monomers.In addition, the acting forces for the binding were hydrogen bonds and van der Waals forces through molecular docking simulation and thermodynamic parameters.All the above results showed that MPS was the stronger quencher and bound to HSA with higher affinity than MMF,therefore it can be better transferred and metabolized in body system.The mechanism of MPS/MMF-HSA interaction has been elucidated, which provides valuable theoretical basis for the clinical use of immunosuppressive drugs.