光谱法、量热法以及分子对接技术研究阿霉素与中心蛋白的作用  

Study of the interaction between doxorubicin and the centrin by spectroscopy,calorimetry and molecular docking techniques

作　　者：张文龙 胡颖媛 任蕾 王颖莉 Zhang Wenlong;Hu Yingyuan;Ren Lei;Wang Yingli(College of Chinese Medicine and Food Engineering,Shanxi University of Chinese Medicine,Jinzhong Shanxi 030619)

机构地区：[1]山西中医药大学中药与食品工程学院,山西晋中030619

出　　处：《山西中医药大学学报》2024年第2期149-153,160,共6页Journal of Shanxi University of Chinese Medicine

基　　金：山西省科技厅项目(201901D211532,202203021212347);山西中医药大学科研基金资助项目(2022PY-TH-06)。

摘　　要：目的:研究阿霉素(doxorubicin,DOX)与八肋游仆虫中心蛋白的N-端部分(N-terminal domain of Euplotes octocarinatus centrin,N-EoCen)的相互作用。方法:采用圆二色光谱以及三维荧光光谱法研究N-EoCen的构象变化,采用稳态荧光光谱法与等温滴定法(ITC)研究DOX与N-EoCen的作用机制,采用分子对接技术模拟DOX与N-EoCen的结合位点。结果:N-EoCen与DOX结合后,构象发生变化,α-helix含量减少。DOX以摩尔比1∶1与N-EoCen结合,结合常数约为105 L/mol。该反应为放热反应,熵变对自由能的贡献较小,反应主要由焓变驱动。结论:DOX主要通过疏水作用、范德华力以及氢键等多种作用与N-EoCen结合,从而使N-EoCen的构象发生改变。Objective:To study the interaction between doxorubicin(DOX)and the N-terminal domain of Euplotes octocarinatus centrin(N-EoCen).Methods:Circular dichroism spectroscopy and three-dimensional fluorescence spectroscopy were used to study the conformational change of N-EoCen.Steady-state fluorescence spectroscopy and isothermal titration calorimetry(ITC)were used to study the interaction mechanism between DOX and N-EoCen.Molecular docking technology was used to simulate the binding site between DOX and N-EoCen.Results:When N-EoCen bound to DOX,the conformation changed and theα-helix content decreased.DOX was bound to N-EoCen at a molar ratio of 1∶1 with a binding constant of about 105 L/mol.The reaction was exthermic,the contribution of entropy change to the free energy was small,and the reaction was mainly driven by enthalpy change.Conclusion:DOX binds to N-EoCen mainly through various interactions such as hydrophobic interaction,van der Waals force and hydrogen bonding,thereby changing the conformation of N-EoCen.

关 键 词：八肋游仆虫中心蛋白 阿霉素 复合物 构象 

分 类 号：O657.3[理学—分析化学]