光谱法与分子模拟技术研究吡唑[3,4-b]并吡啶类衍生物与人血清白蛋白的相互作用  

Study on the mechanism of the interaction of pyrazolo [3,4-b]pyridine derivatives and human serum albumin by spectroscopy and molecular modeling

作　　者：张轶[1,2] 梁晶 冯素玲[1] 张新颖[1] 范学森[1] 贺志安[2] 

机构地区：[1]河南师范大学化学化工学院,河南新乡453007 [2]新乡医学院医学检验系,河南新乡453003 [3]河南省环境监测中心,河南郑州450004

出　　处：《化学研究与应用》2014年第3期346-353,共8页Chemical Research and Application

基　　金：国家自然科学基金项目(21172057)资助

摘　　要：用荧光光谱法和紫外-可见吸收光谱法研究了在模拟人体生理条件下吡唑[3,4-b]并吡啶类药物和人血清白蛋白(HSA)结合反应的特征,并利用同步荧光法和三维荧光法研究了吡唑[3,4-b]并吡啶类药物与HSA作用前后人血清白蛋白的构象变化。研究表明,吡唑[3,4-b]并吡啶类药物对HSA有较强的荧光猝灭作用,该过程为静态猝灭过程。基于荧光猝灭机理,得出不同温度下的结合位点数和结合常数。根据Frster非辐射转移理论可求出吡唑[3,4-b]并吡啶类药物与HSA作用距离;根据基本热力学参数ΔH、ΔS和ΔG判断吡唑[3,4-b]并吡啶类药物和HSA主要通过氢键和范德华力发生相互作用。分子模拟研究结果表明,吡唑[3,4-b]并吡啶类药物与HSA的作用区域位于siteⅠ位(亚结构域ⅡA)。The interaction between pyrazolo[3,4-b] pyridine derivatives and human serum albumin was studied by spectroscopic methods including fluorescence spectra and UV-visible absorption spectra, under simulative physiological conditions. Synchronous fluorescence and three-dimensional fluorescence spectra were used to investigate the structure change of human serum albumin with the addition of pyrazolo[3,4-b]pyridine derivatives. It showed that the intrinsic fluorescence of human serum albumin was quenched by pyrazolo[3,4-b] pyridine derivatives;The main mechanism of protein fluorescence quenching was a static quenching proce-dure. The binding sites number n and apparent binding constant K were measured at different temperatures according to Stern-Volmer equation. The distance between donor（HSA）and acceptor（pyrazolo[3,4-b]pyridine derivatives）was obtained according to Forster theory of non-radiation energy transfer. The thermodynamic parametersΔΗ,ΔG andΔS at different temperatures were calcu-lated,respectively,which indicated that H-bond and Van der Waals played a major role in the interaction of pyrazolo[3,4-b]pyri-dine derivatives with HSA. The results of molecular modeling show that pyrazolo[3,4-b] pyridine derivatives might locate in the subdomain IIA of HSA.

关 键 词：吡唑3 4-b并吡啶类药物 人血清白蛋白 荧光光谱 热力学参数 分子模拟 

分 类 号：O657.3[理学—分析化学]