CAJ | 학술논문

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)。
용형광광보법화자외-가견흡수광보법연구료재모의인체생리조건하필서[3,4-b]병필정류약물화인혈청백단백(HSA)결합반응적특정,병이용동보형광법화삼유형광법연구료필서[3,4-b]병필정류약물여HSA작용전후인혈청백단백적구상변화。연구표명,필서[3,4-b]병필정류약물대HSA유교강적형광졸멸작용,해과정위정태졸멸과정。기우형광졸멸궤리,득출불동온도하적결합위점수화결합상수。근거F?rster비복사전이이론가구출필서[3,4-b]병필정류약물여HSA작용거리；근거기본열역학삼수ΔH、ΔS화ΔG판단필서[3,4-b]병필정류약물화HSA주요통과경건화범덕화력발생상호작용。분자모의연구결과표명,필서[3,4-b]병필정류약물여HSA적작용구역위우siteⅠ위(아결구역ⅡA)。
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.