Study on the thermodynamics of the binding of iminium and alkanolamine forms of the anticancer agent sanguinarine to human serum albumin
Study on the thermodynamics of the binding of iminium and alkanolamine forms of the anticancer agent sanguinarine to human serum albumin
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DOI：
10.1016/j.jct.2011.09.026
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发表时间：
2012-04-01
影响因子：
2.6
通讯作者：
Kumar, Gopinatha Suresh
中科院分区：
文献类型：
--
作者：
Hossain, Maidul;Khan, Asma Yasmeen;Kumar, Gopinatha Suresh
血根碱是一种具有抗癌作用的植物生物碱，可以以带电的亚胺和中性的烷醇胺形式存在。用量热法研究了这两种形式与人血清白蛋白相互作用的热力学，并辅以圆二色性和荧光光谱法研究。热力学结果表明，血红素在HSA上只有一类结合。烷醇胺的平衡常数高4倍（K-a = 2.18）。10(5) M-1)比最小（K-a = 5.97）要好。10 (4) m - 1)。这种结合是由氨的焓驱动的，而烷醇胺的焓为负，熵贡献更大。温度相关的量热数据得到的δ C-p（度）值与两种形式的血碱与HSA络合过程中不同分子力的参与是一致的。荧光猝灭数据提示静态猝灭机制。同步荧光和圆二色性数据与结合时蛋白质的构象变化一致，这种变化对于烷醇胺形式也更高。(C) 2011 Elsevier Ltd.版权所有。
Sanguinarine is an anticancer plant alkaloid that can exist in the charged iminium and neutral alkanolamine forms. The thermodynamics of the interaction of the two forms with human serum albumin was investigated using calorimetric techniques, and the data supplemented with circular dichroism and spectrofluorimetric studies. The thermodynamic results show that there is only one class of binding for sanguinarine on HSA. The equilibrium constant was four times higher for the alkanolamine (K-a = 2.18 . 10(5) M-1) than for iminium (K-a = 5.97 . 10(4) M-1). The binding was enthalpy driven for iminium and favoured by both a negative enthalpy and a stronger favourable entropy contribution for the alkanolamine. Temperature dependent calorimetric data yielded values of Delta C-p(degrees) that are consistent with the involvement of different molecular forces in the complexation of the two forms of sanguinarine to HSA. The fluorescence quenching data suggest a static quenching mechanism. Synchronous fluorescence and circular dichroic data are consistent with a conformational change in the protein on binding that was also higher for the alkanolamine form. (C) 2011 Elsevier Ltd. All rights reserved.