多光谱法结合分子模拟技术研究多西他赛与人血清白蛋白的作用  

The Interaction between Docetaxel and Human Serum Albumin with Spectrometry and Molecular Docking

作　　者：霍彩霞 何丽君 石雷 狄婧 田淑丽 HUO Caixia;HE Lijun;SHI Lei;DI Jing;TIAN Shuli(School of Chemistry and Chemical Engineering,Lanzhou City University,Lanzhou 730070;School of Chemical and Biological Engineering,Lanzhou Jiaotong University,Lanzhou 730070)

机构地区：[1]兰州城市学院化学化工学院,甘肃兰州730070 [2]兰州交通大学化学与生物工程学院,甘肃兰州730070

出　　处：《分析科学学报》2021年第3期329-335,共7页Journal of Analytical Science

基　　金：国家自然科学基金(21765013)。

摘　　要：利用荧光光谱、紫外光谱、三维荧光光谱、红外光谱、圆二色谱和分子对接技术研究了多西他赛(DT)与人血清白蛋白(HSA)的相互作用机理,探讨了7种辅酶对HSA及DT-HSA体系的影响。结果表明,DT对HSA的猝灭机制为静态猝灭且伴随非辐射能量的转移,二者通过疏水力、氢键和范德华力共同作用形成1∶1的配合物。HSA的主要结合位点为亚螺旋域ⅡA siteⅠ,离色氨酸残基更近,几乎不存在药物协同性。随着DT与HSA反应进行,HSA的二级结构α-螺旋含量减少,肽键伸展,疏水基团裸露,构象发生变化。7种辅酶对HSA荧光猝灭效率的影响与对DT和HSA结合的抑制作用一致(维生素B_(2)>辅酶A>维生素C>维生素E>维生素B_(1)>谷胱甘肽>辅酶Q_(10)),但其介入不影响DT对HSA的荧光猝灭机制。The interaction between docetaxel(DT)and human serum albumin(HSA)was investigated with fluorescence spectroscopy,UV spectra,FT-IR spectra,CD and molecular docking.Besides,the fluorescence response of HSA and DT-HSA was researched in presence of seven coenzymes.Results showed that the quenching constants of DT and HSA decreased with the increase of temperature within the set range.Combined with UV spectra,it was confirmed that the quenching effect of DT on the endogenous fluorescence of HSA was static quenching.The number of binding sites n between DT and HSA was approximately equal to 1.The thermodynamic parameters ΔH and ΔS demonstrated that hydrophobic force,hydrogen bond and van der Waals force played important roles in maintaining the stability of the complex.Furthermore,Hill’s coefficients(n_(H)≈1)indicated that there was nearly no cooperative effect.The binding distance(r)was about 1.48 nm,which indicated that the nonradiative energy transfer could probably occur.The primary binding for DT was located at sub-domainⅡA siteⅠof HSA.The results of synchronous fluorescence,three-dimensional fluorescence,FT-IR and CD spectrum further demonstrated that the secondary conformation and microenvironment of HSA changed after interaction with DT.Subsequently,it was found that the effect of seven coenzymes on the quenching efficiency of HSA ordered as follows:Vitamin B_(2)>Coenzyme A>Vitamin C>Vitamin E>Vitamin B_(1)>Glutathione>Coenzyme Q_(10),and simultaneously it had an inhibitory effect on the binding of DT and HSA without affecting the quenching mechanism.This study provided some references for understanding the mechanism of DT-HSA in vivo.

关 键 词：多西他赛 人血清白蛋白 多光谱法 分子对接 

分 类 号：O657.3[理学—分析化学]