盐酸吡格列酮与胰蛋白酶的相互作用分析

Analysis of Intermolecular Interactions Between Pioglitazone Hydrochloride and Trypsin

运用多种光谱法来研究盐酸吡格列酮(PGH)和胰蛋白酶(TRY)的光谱特征。随着PGH的加入,TRY猝灭程度逐渐降低,说明PGH对TRY有一定的猝灭作用,在285,295,310 K下探究得知结合位点数接近于1。热力学常数表明了两者的反应为自发的反应,结合作用力类型通过计算可知为氢键和范德华力。同步荧光光谱表明盐酸吡格列酮使得胰蛋白酶构象发生了变化。根据非辐射能量转移理论得到结合距离r为1.78 nm。金属离子的加入显示Ca^(2+)、Na^(+)、K^(+)、Zn^(2+)与胰蛋白酶之间的作用力比较强产生了竞争,使得盐酸吡格列酮与胰蛋白酶反应体系的结合作用力减弱;Mg^(2+)、Cu^(2+)、Fe^(3+)的加入首先与盐酸吡格列酮反应生成了复合物,再跟胰蛋白酶反应,使得盐酸吡格列酮与胰蛋白酶反应体系的结合作用加强。

The spectral characteristics of pioglitazone hydrochloride(PGH)and trypsin(TRY)were studied by using a variety of spectroscopic methods under physiological conditions close to human body.With the addition of PGH,the TRY quenching degree decreased gradually,indicating that PGH had a certain quenching effect on the TRY,and the number of binding sites was close to 1 after investigation at 285,295 and 310 K.The thermodynamic constants show that the reaction between the two is spontaneous,and the types of binding force can be calculated as hydrogen bond and van der Waals force.Synchronous fluorescence spectra showed that pioglitazone hydrochloride changed the conformation of trypsin.According to the non-radiative energy transfer theory,the binding distance r is 1.78 nm.The addition of metal ions showed that the interaction between Ca ^(2+),Na^(+),K^(+),Zn ^(2+)and trypsin was strong and competitive,which weakened the binding force between pioglitazone hydrochloride and trypsin reaction system.The addition of Mg ^(2+),Cu ^(2+)and Fe ^(3+)first reacted with pioglitazone hydrochloride to form a complex,and then reacted with trypsin,which strengthened the binding effect of pioglitazone hydrochloride with trypsin reaction system.