多光谱法和分子模拟技术研究氟罗沙星与人血清白蛋白的相互作用（英文）

发布时间：2018-03-28 00:11

  本文选题：人血清白蛋白　切入点：氟罗沙星　出处：《光谱学与光谱分析》2017年01期

【摘要】：氟罗沙星(FLRX)是一种含氟喹诺酮类抗菌素,有关它对人血清白蛋白(HSA)的影响及作用机理,特别是对HSA二级结构的影响及内滤光(影响荧光数据的准确性)校正的研究报道较少。采用多光谱法和分子模拟技术探究了FLRX与HSA的相互作用。荧光光谱结果表明,FLRX对HSA的猝灭是由于形成结合常数在105 L·mol~(-1)水平上的1∶1FLRX-HSA基态复合物引起的静态猝灭作用。由Van’t Hoff方程确定的FLRX与HSA结合过程中的ΔH=-107.99kJ·mol~(-1)和ΔS=-240.99J·mol~(-1)·K~(-1),表明FLRX与HSA之间的主要作用力是氢键和范德华力。同步荧光光谱、红外光谱和三维荧光光谱结果表明,静态猝灭过程所产生的中间复合物使HSA的构象发生改变。通过对HSA与FLRX作用前后红外光谱酰胺Ⅰ带进行傅里叶去卷积和分峰拟合,获得代表HSA二级结构的不同子峰,对各子峰进行二级结构归属,根据各子峰的积分面积计算出各二级结构的相对百分含量。结果表明:FLRX与HSA结合后,α-螺旋从51.5%减小到33.2%,β-折叠从30.3%减小到20.7%,β-转角从15.6%增加到33.6%。取代实验显示FLRX与HSA的结合位点在HSA的siteⅠ(亚域ⅡA)。分子对接实验结果表明,FLRX可以通过氢键、疏水作用和范德华力等多种作用力很好的结合在亚域ⅡA的疏水腔中。实验获得的可信数据将有助于阐明FLRX与HSA的作用机制,也有助于理解FLRX在储运过程中对蛋白质功能的影响。
[Abstract]:Fleroxacin (FLRX) is a fluoroquinolone antibiotic. The effect of FLRX on human serum albumin (HSA) and its mechanism of action are discussed. Especially, the influence of secondary structure of HSA and the correction of internal filter (affecting the accuracy of fluorescence data) were seldom reported. The interaction between FLRX and HSA was studied by means of multispectral method and molecular simulation. The quenching of HSA is caused by the formation of 1:1FLRX-HSA ground state complexes at the binding constant of 105L mol / L. The 螖 H=-107.99kJ molanine (-1) and 螖 Sn-240.99J molan-1 (K-1) determined by the Van't Hoff equation in the binding process between FLRX and HSA indicate that the main mechanism between FLRX and HSA is the formation of the FLRX / HSA complex at the level of 105L / mol ~ (-1), indicating that the interaction between FLRX and HSA is mainly due to the interaction between FLRX and HSA. Force is hydrogen bond and van der Waals force. Synchronous fluorescence spectrum, The results of IR and 3D fluorescence spectra showed that the conformation of HSA was changed by the intermediate complex produced by static quenching process. The Fourier deconvolution and peak fitting of the amide I band of IR spectrum before and after the interaction of HSA with FLRX were carried out. Different sub-peaks representing the secondary structure of HSA were obtained, and the secondary structure of each sub-peak was assigned. According to the integral area of each sub-peak, the relative percentage content of each secondary structure is calculated. The results show that the 伪 -helix decreases from 51.5% to 33.2%, the 尾 -fold decreases from 30.3% to 20.7 and the 尾 -rotation angle increases from 15.6% to 33.6um after combining with HSA. The molecular docking results showed that the molecular docking site of HSA could be obtained by hydrogen bonding. The hydrophobic interaction and van der Waals force are well combined in the hydrophobic cavity of subdomain 鈪，

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