嘧啶衍生物与人血清白蛋白的相互作用

发布时间：2018-04-25 20:31

本文选题：人血清白蛋白 + 嘧啶衍生物　；参考：《高等学校化学学报》2017年11期

【摘要】：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.
[Abstract]:Under simulated physiological conditions, using fluorescence spectra, Laser flash photolysis (LFP) and molecular docking techniques were used to study the interaction of eight pyrimidine derivatives, PDs A 5-FU, with human serum albumin (HSA). The fluorescence quenching mechanism of HSA by PDs was analyzed by Stern-Volmer equation and laser flash photolysis technique. PDs A and B were static quenched PDs G and H were dynamically quenched. The binding constant Ka and binding site number nof five kinds of PDs and HSA were obtained by the method of double reciprocal curve. The binding sites of five kinds of PDs to the carrier were all 1, and all of them were bound by weak binding force. Based on the thermodynamic parameters 螖 H, 螖 S and 螖 G, it is inferred that the interaction between PDs C and E and HSA is electrostatic force and hydrophobic force. The interaction force between PDs A and D and HSA is hydrogen bond and van der Waals force, and the molecular docking results are consistent. The binding distance between HSA and PDs is analyzed based on the F9rster non-radiative energy transfer theory. The results are less than 4 nm and accord with the energy transfer theory. Furthermore, the spatial conformation of HSA during the binding of PDs to HSA was investigated by synchronous fluorescence, three-dimensional fluorescence and circular dichroism. The results showed that only PDs A and C enhanced the hydrophobicity of HSA aromatic amino acids. The results of in vitro experiments show that HSA can be used as a good carrier for transport and storage of PDs Alae, which provides reference experimental data for the further study of pyrimidine derivatives.
【作者单位】：大连大学生命科学与技术学院;大连大学辽宁省生物有机化学重点实验室;大连大学环境与化学工程学院;
【基金】：国家自然科学基金(批准号:21271036,21571025,21601023,21601024,21601025,21506018)资助~~
【分类号】：O657.3;R96

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