光谱及分子模拟法对HSA和BSA与酪氨酸激酶抑制剂Imatinib相互作用的比较分析

发布时间：2018-07-24 20:53

【摘要】：研究一种酪氨酸激酶抑制剂(tyrosine kinase inhibitor,TKI)伊马替尼(imatinib,IMA)与人血清清蛋白(HSA)及牛血清清蛋白(BSA)的相互作用,比较分析HSA和BSA与IMA相互作用机制的差异.模拟生理条件下,计算机模拟技术结合荧光光谱和紫外光谱法,研究IMA与蛋白质的作用机制.分子模建IMA与血清清蛋白的结合模型,表明伊马替尼与蛋白质的相互作用力为疏水作用力,兼有氢键作用.光谱结果表明,IMA与HSA和BSA的相互作用表现为静态结合过程,结合强度较强,IMA与HSA和BSA分子的结合距离r值较小,说明发生了能量转移现象.IMA对HSA和BSA的结构域微区构象产生影响,使结合位域的疏水性发生改变.荧光相图技术解析出IMA与HSA和BSA反应构象型态的变迁为"二态"模型.HSA与IMA相互作用的热力学参数表明,IMA与HSA之间是以疏水作用为主的分子间作用,而IMA与BSA之间的作用力为氢键和范德华力,兼有少量的疏水作用力.光谱实验与计算机模拟结果基本一致,可为研究IMA与HSA和BSA相互作用本质提供一定参考.
[Abstract]:To study the interaction between (tyrosine kinase inhibitor and human serum albumin (HSA) and bovine serum albumin (BSA), a tyrosine kinase inhibitor (tyrosine kinase inhibitor), and to compare and analyze the mechanism of interaction between HSA and BSA and IMA. Under simulated physiological conditions, the interaction mechanism between IMA and protein was studied by computer simulation combined with fluorescence spectrum and ultraviolet spectroscopy. The molecular model of IMA binding to serum albumin indicates that the interaction force between imatinib and protein is hydrophobic and hydrogen bonding. The spectral results show that the interaction of ima with HSA and BSA is a static binding process, and the binding distance r value of HSA and BSA molecules is smaller than that of ima, and the binding strength of IMA is stronger than that of HSA and BSA molecules. It is shown that the energy transfer phenomenon occurred .IMA has an effect on the conformation of HSA and BSA domains, which changes the hydrophobicity of binding sites. Fluorescence phase diagram analysis shows that the transition of conformation of IMA with HSA and BSA is a "two-state" model. The thermodynamic parameters of the interaction between IMA and IMA indicate that the hydrophobic interaction between HSA and IMA is a hydrophobic intermolecular interaction. The interaction force between IMA and BSA is hydrogen bond and van der Waals force with a small amount of hydrophobic force. The results of spectral experiments are consistent with those of computer simulation, which can be used as a reference for the study of the nature of interaction between IMA and HSA and BSA.
【作者单位】：浙江农林大学理学院;
【基金】：国家自然科学基金项目(No.20877072)资助浙江省自然科学基金项目(No.Y2100458)资助~~
【分类号】：R969.2;O657.3

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