2,3,3'-三氯联苯与人血清白蛋白之间相互作用的计算模拟及光谱研究

利用分子对接、分子动力学模拟、荧光光谱、紫外光谱及同步荧光光谱法研究了2,3,3'-三氯联苯(PCB-20)与人血清白蛋白(HSA)的相互作用。分子对接结果表明,PCB-20与HSA通过疏水作用力稳定结合于HSA的疏水空腔内。光谱法实验结果表明,PCB-20通过与HSA形成HSA-PCB20复合物从而对HSA具有荧光猝灭作用,猝灭原因是静态猝灭和非辐射能量转移,热力学参数也表明两者结合的主要驱动力为疏水作用力,计算模拟与实验结果吻合度较高。分子动力学模拟结果表明,PCB-20能够与HSA稳定结合,且与同步荧光光谱实验共同证明其对HSA的构象变化产生了一定影响。     

2,3,3′-三氯联苯与人血清白蛋白之间相互作用的计算模拟及光谱研究

利用分子对接、分子动力学模拟、荧光光谱、紫外光谱及同步荧光光谱法研究了2,3,3′-三氯联苯(PCB-20)与人血清白蛋白(HSA)的相互作用。分子对接结果表明,PCB-20与HSA通过疏水作用力稳定结合于HSA的疏水空腔内。光谱法实验结果表明,PCB-20通过与HSA形成HSA-PCB20复合物从而对HSA具有荧光猝灭作用,猝灭原因是静态猝灭和非辐射能量转移,热力学参数也表明两者结合的主要驱动力为疏水作用力,计算模拟与实验结果吻合度较高。分子动力学模拟结果表明,PCB-20能够与HSA稳定结合,且与同步荧光光谱实验共同证明其对HSA的构象变化产生了一定影响。     

杜鹃素新结构衍生物与人血清白蛋白相互作用的光谱及分子对接

采用光谱法及分子对接法考察了该化合物与人血清白蛋白(HSA)的相互作用。荧光光谱分析表明,DJS-NO_2对HSA的荧光有明显的猝灭作用,其机制属于静态荧光猝灭;温度为25℃和37℃时,猝灭常数分别为6.691×10~(13)mol/(L·s)和3.433×10~(13)mol/(L·s);结合常数分别为4.914×10~5mol/L和4.610×10~5mol/L,具有一个结合位点。热力学分析表明,该化合物与HSA之间的结合以疏水作用力为主;三维荧光光谱分析表明DJS-NO_2导致HSA氨基酸残基微环境和二级构象发生变化。圆二色谱分析显示二者的结合使得HSA的α-螺旋含量减少,提示HSA构象发生变化。分子模拟结果显示DJS-NO_2主要与HSA的位点I结合,且该化合物通过氢键与ALA118结合最紧密。     

噻螨酮与人血清白蛋白的作用机制

用分子对接方法及紫外-可见吸收光谱、同步荧光光谱、三维荧光光谱等实验手段研究了噻螨酮(HEX)与人血清白蛋白(HSA)的相互作用及对HSA构象的影响.预测结果表明,HEX能与HSA发生相互作用,且作用位点site II比site I的打分小约4.5.实验结果表明,HEX猝灭HSA的内源荧光且作用机制为静态猝灭;HEX使HSA周围的微环境发生变化,导致蛋白质的肽链结构改变;298和291 K时HEX与HSA相互作用的结合常数(KA)和结合位点数分别为7.35×103 mol/L、0.82和1.02×104 mol/L、0.86,证实HEX仅在site II存在作用位点;HEX与Trp214的结合距离为3.01 nm,作用力主要为氢键、范德华力和疏水作用力.这些研究所获得的多种信息有助于在分子水平上理解农药对人体造成的毒性及可能的生物累积性.     

光谱法研究盐酸麻黄碱及盐酸伪麻黄碱与人血清白蛋白的键合

在模拟人体生理条件下,采用紫外光谱法、荧光光谱法和同步荧光光谱法研究盐酸麻黄碱及盐酸伪麻黄碱与人血清白蛋白(HSA)的结合作用.实验表明:盐酸麻黄碱和盐酸伪麻黄碱对HSA的荧光猝灭机制均为静态猝灭,盐酸麻黄碱和盐酸伪麻黄碱与HSA均形成1∶1复合物,结合常数K分别为2.53×104 L·mol-1和2.02×104 L...     

光谱法研究根皮苷与人血清白蛋白相互作用

在模拟生理条件下,采用荧光光谱、紫外光谱和同步荧光光谱法研究了根皮苷(Phlorizin)与人血清白蛋白(HSA)的相互作用。结果表明:根皮苷能使HSA发生内源荧光猝灭,属静态猝灭。在293、303 K和313 K下,根皮苷与HSA的结合常数分别为3.163 5×105、1.774 8×105、1.193 5×105L.mol-1,结合位点数n近似为1;热力学分析表明根皮苷与HSA间的结合力为氢键及范德华力;根据Frster非辐射能量转移理论求得二者结合距离为3.97 nm;同步荧光光谱表明根皮苷主要与HSA中的色氨酸残基发生相互作用,改变色氨酸周围的局部构象;金属离子的介入会影响根皮苷与HSA的结合能力。     

分子荧光光谱法结合分子动力学模拟研究2′-OH-BDE-68与HSA的相互作用

结合分子荧光光谱法、分子对接和分子动力学模拟等方法研究了在生理条件(pH 7.40)下2′-羟基-2,3′,4,5-四溴二苯醚(2′-OH-BDE-68)与人血清白蛋白(HSA)的相互作用及其对HSA构象的影响。结果表明:1 2′-OH-BDE-68对HSA内源性荧光的猝灭属静态猝灭和非辐射能量转移过程;2两者之间的反应是以疏水作用力为主辅以微弱的静电作用的自发反应过程;3 2′-OH-BDE-68与HSA的结合在10ns内趋于平衡,结合位点在SiteⅠ;4复合物的形成使HSA分子中的色氨酸的疏水性增加,从而HSA的二级结构发生改变。     

光谱法研究N-丁基-N ＇-(对氨基苯磺酸钠)硫脲与人血清白蛋白的相互作用及其分析应用

利用荧光光谱法和紫外光谱法研究了模拟生理条件下N-丁基-N＇-(对氨基苯磺酸钠)硫脲(BPT)与人血清白蛋白(HSA)的相互作用.研究结果表明,BPT对HSA内源荧光的猝灭是静态猝灭.由热力学参数确定了BPT与HSA间存在疏水作用,根据Firster能量转移理论计算出结合距离为2.97 nm.通过三维荧光光谱研究了BP...     

2,4,6-三氯苯酚与人血清白蛋白相互作用的研究

运用荧光光谱、紫外吸收光谱、循环伏安法和计算机模拟分子对接技术,研究了2,4,6-三氯苯酚(TCP)与人血清白蛋白(HSA)的相互作用。研究结果表明,TCP与HSA相互结合形成了复合物,且该复合物不具有荧光和电化学活性。TCP通过静态猝灭的方式引起HSA内源荧光的猝灭,并对其构象有一定影响,在温度为300、305、310和315K下,二者的结合常数KA分别为1.702×10~5、3.681×10~6、1.520×10~5和1.335×10~5 L·mol~(–1),平均结合位点数n约为1。TCP在HSA的亚结构域ⅡA中通过疏水和静电共同作用形成稳定的复合物。在研究温度下Hill系数nH值略微大于1,说明TCP间呈现微弱的正协同作用。柠檬酸和维生素C的介入未改变TCP对HSA的猝灭类型,但二者的结合常数和结合位点数急剧降低,严重削弱了TCP与HSA的结合能力。     

甲基橙皮苷和人血清白蛋白相互作用的光谱研究

利用荧光光谱法和红外光谱法研究了甲基橙皮苷(MH)与人血清白蛋白(HSA)的相互作用.结果表明,MH对HSA的荧光有较强的猝灭作用.在296、303、310K温度下,MH与HSA相互作用的结合常数分别为1.77×104,2.65×104,3.53×104 L·mol-1.热力学分析结果表明,MH与HSA之间的结合过程是吸热的并且是自发的;作用力以疏水作用为主,并伴随氢键作用.     

吡虫啉与人血清白蛋白相互作用热力学行为

在模拟人体生理条件下,综合利用荧光光谱、紫外吸收光谱、圆二色谱和分子模拟等方法,研究了吡虫啉(IMI)和人血清白蛋白(HSA)相互作用的热力学行为。荧光光谱和紫外吸收光谱的分析表明：吡虫啉能有效猝灭HSA的内源荧光,猝灭机制为静态猝灭;通过所获取的相互作用热力学参数,可知两者之间的相互作用是一个吉布斯自由能降低的自发过程,且二者之间的主要作用力为氢键和范德华力。位点竞争实验和分子模拟的结果表明：吡虫啉在HSA的主要结合位置为位点?。圆二色谱、同步荧光光谱和三维荧光的分析发现：吡虫啉引起HSA的构象发生改变,其α-螺旋含量降低,无规卷曲含量升高,肽链结构在吡虫啉的作用下有所伸展。     

多光谱法和分子对接模拟法研究黄腐酸与胃蛋白酶的相互作用

利用荧光光谱、 同步荧光光谱、 三维荧光光谱、 紫外-可见吸收光谱、 傅里叶变换红外光谱和圆二色光谱以及分子对接模拟方法研究了黄腐酸(FA)与胃蛋白酶(PEP)之间的相互作用. 荧光光谱分析表明, FA-PEP荧光猝灭的类型为静态猝灭. 根据Stern-Volmer方程和静态猝灭双对数公式计算得到猝灭常数K_sv和结合位点数n. 根据Vant’t Hoff方程计算得到热力学常数ΔH=-59.86 kJ/mol, ΔS=-98.13 J·mol ^-1·K ^-1, ΔG=-30.62 kJ/mol(298 K). 热力学分析表明, 氢键和范德华力是PEP与FA之间的主要结合力, 其反应为自发过程. 根据F?rster非辐射能量转移理论, 计算得到PEP和FA之间的结合距离为2.436 nm, 表明在FA与PEP之间发生了非辐射能量转移. 三维荧光光谱分析表明, 在FA存在下PEP的肽链骨架结构发生了改变. 此外, 紫外-可见吸收光谱、 同步荧光光谱和红外光谱结果表明, FA使PEP的二级构象发生变化. 分子对接模拟结果表明, FA引起PEP荧光猝灭的结合作用力不仅有氢键和范德华力, 还有疏水作用力.     

嘧啶衍生物与人血清白蛋白的相互作用

在模拟生理条件下,运用荧光光谱、激光闪光光解(LFP)和分子对接等技术研究了8种具有抗肿瘤活性的嘧啶衍生物(PDs,其中PDs A 5-FU为成药,PDs B-H为实验室自制)与人血清白蛋白(HSA)的相互作用.利用Stern-Volmer方程和激光闪光光解技术分析了PDs对HSA的荧光猝灭机制,PDs A和B为静态猝灭,PDs G和H为动态猝灭.用双倒数曲线法得出5种PDs与HSA的结合常数Ka和结合位点数n,在测定条件下5种PDs与载体结合位点数均为1,且均以弱结合力结合,通过热力学参数ΔH,ΔS和ΔG推测出PDs B,C和E与HSA之间的作用力为静电作用力和疏水作用力,PDs A和D与HSA之间的作用力是氢键和范德华力,分子对接结果与其一致.根据F9rster非辐射能量转移理论(FRET)分析了HSA和PDs之间的结合距离(r),其结果均小于4 nm,符合能量转移理论.进一步利用同步荧光、三维荧光和圆二色光谱考察了PDs与HSA结合过程中HSA空间构象的变化,结果显示,仅PDs A和C对HSA的芳香族氨基酸周围的疏水性略有增强作用.体外实验结果表明,HSA可以作为优良的载体来运输和储存PDs A~E,这为嘧啶衍生物的后续研究提供了可参考的实验数据.     

Studies of the Interaction Between Ronidazole and Human Serum Albumin by Spectroscopic and Molecular Docking Methods

Ronidazole (RNZ) is widely used for the therapeutic treatment of farmed animals and is suspected of being a human carcinogen and mutagen. The interaction between RNZ and human serum albumin (HSA) was investigated systematically by fluorescence spectroscopy, synchronous fluorescence, three-dimensional fluorescence, CD spectroscopy, UV–vis absorption spectroscopy and a molecular docking study. The results indicate that the probable quenching mechanism of HSA by RNZ is dynamic quenching. The corresponding thermodynamic parameters, such as ΔH, ΔS and ΔG, etc., were calculated according to the van’t Hoff equation. The results indicate that the forces acting between RNZ and HSA are mainly hydrogen bonds and van der Waals forces. The conformational changes in the interaction were studied by synchronous fluorescence, CD spectroscopy and three-dimensional fluorescence spectra. The results reveal that the microenvironment and conformation of HSA has been changed. A molecular modeling study further confirmed the binding mode obtained by the experimental studies.     

Investigation of nitroxoline-human serum albumin interactions by spectroscopic methods

Nitroxoline is a wide spectrum antibacterial and is one of the most important urinary antiseptics.The interaction between nitroxoline and human serum albumin(HSA)has been investigated systematically by fluorescence spectroscopy,synchronous fluorescence,three-dimensional fluorescence,CD spectroscopy and UV-Vis absorption spectroscopy.The results indicated that the quenching of HSA by nitroxoline was static.The corresponding thermodynamic parameters △H,△S and △G calculated according to van’t Hoff equation revealed that the intermolecular forces acting between nitroxoline and HSA were mainly hydrogen bonding and van der Waals forces.The conformational changes in the interaction were studied by synchronous fluorescence,CD spectroscopy and three-dimensional fluorescence spectra which showed changes in the microenvironment and conformation of HSA.     

BCBP与牛血清白蛋白相互作用热力学

塞来昔布衍生物是一类应用非常广泛的治疗急慢性炎症的新型非甾体抗炎药。本文综合利用荧光光谱、紫外吸收光谱、圆二色谱和分子模拟等方法,研究了塞来昔布衍生物1-苯磺酰胺-3-羧基-5-苯基吡唑(BCBP)与牛血清白蛋白(BSA)相互作用的热力学行为。荧光光谱和紫外吸收光谱的分析表明：BCBP能有效猝灭BSA的内源荧光,猝灭机制为静态猝灭。通过所获取的相互作用热力学参数,可知两者之间的相互作用是一个吉布斯自由能降低的自发过程,且二者之间的主要作用力为氢键和范德华力。圆二色谱的分析发现BCBP引起BSA的构象发生改变,其α-螺旋含量降低,无规卷曲含量升高。分子对接的结果与实验结果相符。     

N,N-二甲基吡啶苯甲醛缩对二甲氨基苯甲酰腙的合成及对Cu2+的选择性识别

设计合成了可用于识别铜离子的化合物N,N-二甲基吡啶苯甲醛缩对二甲氨基苯甲酰腙(1), 通过¹H NMR, ¹³C NMR和MS等对其结构进行了表征; 采用荧光光谱和吸收光谱法研究了化合物1与金属离子间的相互作用. 结果表明, 化合物1对Cu²⁺ 呈现良好的选择性, Cu²⁺ 的加入使化合物1的荧光强度增强12.5倍, 加入其它金属离子如Fe³⁺, Zn²⁺, Pb²⁺, Hg²⁺, Cd²⁺, Co²⁺, Ni²⁺, Li⁺, K⁺, Ca²⁺, Mg²⁺ 和 Ag⁺, 仅引起化合物1荧光强度的微降. 采用双倒数线性回归拟合法计算可知, 化合物1与Cu²⁺ 形成了1: 1型强发光配合物, 结合常数为2.0×10⁷ L/mol.     

Preparation of (2E)-3-(4'-Halophenyl)prop-2-enoyl Sulfachlorpyridazine Sodium Salts and Their Interaction with Bovine Serum Albumin by Fluorescence Spectroscopy

Three (2E)-3-(4'-halophenyl)prop-2-enoyl sulfachlorpyridazine sodium salts(XPSCA) were synthesized. Their chemical structures were confirmed by ¹H NMR and ¹³C NMR, electrospray ionization mass spectrometry (ESI-MS), and infrared(IR) spectroscopy. The interactions between XPSCA and bovine serum albumin(BSA) were investigated under imitated physiological condition by fluorescence quenching technique and UV-Vis absorption spectroscopy according to the Stern-Volmer equation. The results from the emission quenching at different temperatures indicate that the quenching mechanism of serum albumin by XPSCA was static quenching mechanism at low XPSCA concentrations or a combined quenching(static and dynamic) mechanism at higher XPSCA concentrations. At different temperatures, the binding constant and the binding sites of XPSCA with BSA were investigated, and the distances were evaluated according to Förster non-radiative resonance energy transfer theory. The thermodynamic parameters were calculated according to van't Hoff equation, which implies that both van der Waals interaction and hydrogen bond played major roles in stabilizing the XPSCA-BSA complexes, whereas hydrophobic interactions were secondary. Moreover, the conformational changes in BSA were analyzed by synchronous fluorescence spectra.     

Investigating the interaction of juglone (5-hydroxy-1, 4-naphthoquinone) with serum albumins using spectroscopic and in silico methods

The interaction between juglone at the concentration range of 10–110 µM and bovine serum albumin (BSA) or human serum albumin (HSA) at the constant concentration of 11 µM was investigated by fluorescence and UV absorption spectroscopy under physiological-like condition. Performing the experiments at different temperatures showed that the fluorescence intensity of BSA/HSA was decreased in the presence of juglone by a static quenching mechanism due to the formation of the juglone–protein complex. The binding constant for the interaction was in the order of 10³ M^?1, and the number of binding sites for juglone on serum albumins was determined to be equal to one. The thermodynamic parameters including enthalpy (ΔH), entropy (ΔS) and Gibb’s free energy (ΔG) changes were obtained by using the van’t Hoff equation. These results indicated that van der Waals force and hydrogen bonding were the main intermolecular forces stabilizing the complex in a spontaneous association reaction. Moreover, the interaction of BSA/HSA with juglone was verified by UV absorption spectra and molecular docking. The results of synchronous fluorescence, UV–visible and CD spectra demonstrated that the binding of juglone with BSA/HSA induces minimum conformational changes in the structure of albumins. The increased binding affinity of juglone to albumin observed in the presence of site markers (digoxin and ibuprofen) excludes IIA and IIIA sites as the binding site of juglone. This is partially in agreement with the results of molecular docking studies which suggests sub-domain IA of albumin as the binding site.