多光谱技术结合分子模拟研究头孢唑林和头孢曲松与人血清白蛋白的相互作用

发布时间：2018-03-16 18:18

本文选题：头孢曲松　切入点：头孢唑林　出处：《光谱学与光谱分析》2017年04期 　论文类型：期刊论文

【摘要】：头孢唑林(CFZ)属第一代β-内酰胺类半合成头孢菌素,对革兰氏阳性菌和革兰氏阴性菌均有较强的抗菌作用。头孢曲松(CRO)属第三代β-内酰胺类广谱抗生素,对敏感致病菌导致的疾病及手术后期感染预防有一定作用。人血清白蛋白(HSA)作为生物体内循环系统中含量最丰富的蛋白质,可以与多种内源性和外源性化合物可逆性结合,起到储存和转运的作用。因此,研究CFZ和CRO与HSA的相互作用对了解CFZ和CRO的药代动力学行为具有重要意义。在模拟生理条件下,采用多种光谱法和分子对接技术研究CFZ和CRO与HSA的相互作用。结果表明,在298和310K条件下,CFZ和CRO与HSA分别形成复合物导致内源荧光猝灭,猝灭机制均为静态猝灭。在消除内滤光影响下,HSA-CFZ和HSA-CRO体系的猝灭常数(KSV)和结合常数(Ka)均随着温度的升高而降低,结合位点数约为1。根据F錸ster能量转移定律,CFZ和CRO与HSA结合距离分别为2.41和1.40nm。希尔系数(nH)值小于1,表明CFZ和CRO分别与HSA结合后存在药物间负协同作用。热力学参数(ΔH_(HSA-CFZ)=-22.67kJ·mol~(-1),ΔH_(HSA-CRO)=-39.56kJ·mol~(-1),ΔS_(HSA-CFZ)=-4.90J·mol~(-1)·K~(-1),ΔS_(HSA-CRO)=-37.28J·mol~(-1)·K~(-1))揭示,CFZ和CRO能自发地通过氢键和范德华力与HSA相结合。三维荧光光谱和圆二色谱法(CD)显示CFZ和CRO使HSA的微环境和构象发生改变。分子对接技术显示CFZ和CRO均结合在HSA的siteⅠ结合位点上,与取代实验结果一致。本研究有助于了解CFZ和CRO在机体内的作用机制及对HSA结构和功能的影响。
[Abstract]:Cefazolin (CFZ) belongs to the first generation of 尾 -lactam semisynthetic cephalosporins and has a strong antibacterial effect against Gram-positive and Gram-negative bacteria. Ceftriaxone (CRO) belongs to the third generation of 尾 -lactam broad-spectrum antibiotics. Human serum albumin (HSA), as the most abundant protein in the circulatory system, can bind to many endogenous and exogenous compounds. Therefore, it is important to study the interaction between CFZ and CRO and HSA to understand the pharmacokinetic behavior of CFZ and CRO. The interaction of CFZ and CRO with HSA was studied by means of various spectroscopic methods and molecular docking techniques. The results showed that the formation of complexes between CFZ and CRO and HSA at 298 and 310 K resulted in endogenous fluorescence quenching, respectively. The quenching mechanism was static quenching. The quenching constants of HSA-CFZ and HSA-CRO decreased with the increase of temperature. The binding sites are about 1. According to the energy transfer law of F rhenium ster, the binding distance between HSA and CFZ is 2.41 and 1.40 nm, respectively. The Hill coefficient is less than 1, which indicates that there is a negative synergistic effect between CFZ and CRO after binding to HSA. (螖 HSA-CFZU -22.67 kJ 路mol-1C, 螖 HSA-CROU -39.56 kJ 路mol-1, 螖 SSA-CFZU -4.90 J 路mol-l) 路K-1, 螖 SSA-CROU -37.28 J 路mol-1) 路K ~ (-1) revealed that CFZ and CRO could spontaneously combine with HSA through hydrogen and van der Waals force. Three-dimensional fluorescence spectra and circular dichroic chromatography showed that CFZ and CRO changed the microenvironment and conformation of HSA. Molecular docking techniques showed that CFZ and CRO were both CFZ and CRO. Binding to the site I binding site of HSA, This study is helpful to understand the mechanism of CFZ and CRO in vivo and the effect on the structure and function of HSA.
【作者单位】：中央民族大学生命与环境科学学院;中央民族大学北京市食品环境与健康工程技术研究中心;
【基金】：国家自然科学基金项目(21177163) 高等学校学科创新引智计划项目(B08044) 中央民族大学一流大学一流学科建设项目(YLDX01013);中央民族大学学术团队建设项目(2015MDTD25C&13C) 建设世界一流大学(学科)和特色发展引导专项资金(2016) 2015年统筹推进一流大学和一流学科建设经费(10301-0150200604) 一流大学一流学科建设过渡性经费专项资金项目(2016,博士)资助
【分类号】：R96;O657.3

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