吡喃并[3,2-c]吡啶酮-嘧啶核苷杂化体与白蛋白相互作用的光谱和分子模拟研究

Study on the interaction between hybrids of pyrimidine nucleoside pyranopyridone and serumim album by spectrometry and molecular modeling methods

在模拟生理条件下,用荧光、紫外吸收光谱法及分子模拟研究了具有抗病毒活性的吡喃并[3,2-c]吡啶酮-嘧啶核苷杂化体—3,′5′-二-O-乙酰基-5-[2-氨基-7-甲基-5-氧代-5,6-二氢-4H-吡喃并[3,2-c]吡啶-3-氰基]-2′-脱氧尿苷(PPNH)与牛血清白蛋白(BSA)的相互作用。PPNH对牛血清白蛋白的荧光猝灭为动态猝灭。由热力学参数推断出二者主要靠疏水作用力发生相互作用。根据F rster非辐射能量转移理论,确定了给体-受体间的作用距离。同步荧光光谱表明PPNH使色氨酸残基的疏水性增强,酪氨酸残基的亲水性增强,BSA的构象发生变化。用分子对接技术对PPNH与血清白蛋白之间的相互作用从分子水平上进行预测,推断出PPNH主要位于血清白蛋白亚结构域IIA中,分子对接结果与实验结果基本一致。

The interaction between bovine serum albumin（BSA） and hybrids of pyrimidine nucleoside pyranopyridone,3′,5′-oli-o-acetyl-5-[2-amino-7-methyl-5-oxo-5,6-dihydro-4H-pyranopyridine-3-cyano]-2′-deoxy uridine（PPNH） with antiviral activity,was studied by fluorescence and ultra-violet absorption spectroscopies under the physiological conditions,combined with molecular modeling method.It was found that PPNH caused the fluorescence quenching of BSA through a dynamic quenching.It was concluded that hybrids PPNH interacted mainly with BSA mainly by the hydrophobic force according to the thermodynamic parameters.The distance between donor and the acceptor was calculated according to Frster theory of non-radiation energy transfer.The synchronous fluorescence spectra displayed that PPNH changed the conformation of BSA,resulting in the increase of the hydrophobicity around the tryptophan residues and the increase of hydrophilicity around Tyrosine.Furthermore,using the molecular modeling method,the interaction between them was predicted from molecular angle.PPNH might locate in the subdomain IIA of HSA.The results of molecular modeling analysis were in agreement with experimental results.