5-羟甲基糠醛与不同血清白蛋白的结合反应机制研究

利用光谱实验结合计算机模拟技术研究中药活性成分5-羟甲基糠醛 (5-HMF) 与人血清白蛋白 (HSA) 及牛血清白蛋白 (BSA) 的结合反应机制。结果表明, 5-HMF与HSA及BSA均结合生成静态复合物, 但结合强度存在一定的差异, 5-HMF与HSA及BSA分子的结合距离不同, 且r值均很小, 说明发生了能量转移现象。药物分子与血清白蛋白 (SA) 相互作用过程中, 药物分子对HSA及BSA构象均产生影响, 使结合位域的疏水性发生改变, 但对不同血清白蛋白影响程度迥异。应用荧光相图法解析出5-HMF与BSA及HSA反应构象形态的变迁均为“二态”模型。金属离子Co (Ⅱ) 介导药物与SA相互作用的程度随SA种类不同而存在差别。依据计算机模拟建立的分子对接结果显示, 5-HMF与血清白蛋白的相互作用主要为疏水作用和氢键, 分子模拟结果与光谱实验结果一致, 此为5-HMF的药理作用机制研究提供一定理论参考。

Binding mechanism of traditional Chinese medicine active component 5-hydroxymethyl-furfural and HSA or BSA

A combination of spectral experiment and molecular modeling techniques has been used to characterize the binding mechanism between an active component 5-hydroxymethyl-furfural (5-HMF) of traditional Chinese medicine and human serum albumin (HSA) or bovine serum albumin (BSA). The interaction mechanism of 5-HMF binding with HSA/BSA is analyzed. Although the drug can bind with HSA/BSA to form stable complexes, there are some differences in the bond strength. The values of binding distances (r) are different and low, which indicated the occurrence of energy transfer. The drug had conformational effect on HSA/BSA, which resulted in different changes of hydrophobic environment of the binding domain in HSA/BSA. The 'phase diagram' of fluorescence revealed that the changes on the conformational pattern of proteins have been affected by drug conformed to the "all-or-none" pattern. The interactions between drug and protein influenced by Co(II) were also discussed. Its effects acting on 5-HMF-HSA/BSA interactions are different. The computational modeling method was used to study the interaction between 5-HMF and HSA/BSA. The results of molecular model studies revealed that the binding modes for drug-serum albumin systems are mainly hydrophobic interactions and hydrogen bonding. These results are in accordance with spectral results. The research results have given a better theoretical reference for the study of pharmacological mechanism of 5-hydroxymethyl-furfural.