论文部分内容阅读
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.
To investigate the interaction between imatinib (IMA) and human serum albumin (HSA) and bovine serum albumin (BSA), a tyrosine kinase inhibitor (TKI) And IMA.The mechanism of interaction between IMA and protein was studied by computer simulation and fluorescence spectroscopy and ultraviolet spectroscopy under the condition of simulated physiological conditions.The molecular modeling of IMA and serum albumin binding model showed that imatinib and The interaction between protein and BSA is hydrophobic, and hydrogen bonding is also observed.The spectral results show that the interaction between IMA and HSA and BSA is static binding, the binding strength is strong, the binding distance between IMA and HSA and BSA is r Is smaller, indicating that energy transfer phenomenon occurred.IMA on the HSA and BSA domain microstructure conformation affect the hydrophobicity of the binding site changes.Fluid phase diagram technology to resolve the IMA and HSA and BSA reaction conformational patterns The thermodynamic parameters of the interaction between HSA and IMA indicate that there is an intermolecular interaction dominated by hydrophobic interaction between IMA and HSA, while the interaction between IMA and BSA is hydrogen bond and van der Waals Force, both a small amount Hydrophobic force.The spectral experiment and computer simulation results are basically the same, which can provide some reference for studying the essence of the interaction between IMA and HSA and BSA.