Binding of berberine to human telomeric quadruplex - spectroscopic, calorimetric and molecular modeling studies
Binding of berberine to human telomeric quadruplex - spectroscopic, calorimetric and molecular modeling studies
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DOI：
10.1111/j.1742-4658.2008.06541.x
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发表时间：
2008-08-01
期刊：
影响因子：
5.4
通讯作者：
Maiti, Souvik
中科院分区：
文献类型：
--
作者：
Arora, Amit;Balasubramanian, Chandramouli;Maiti, Souvik
本研究考察了黄连素与人端粒d[AG(3)(T(2)AG(3))(3)]四链的结合特性。通过紫外-可见光谱、荧光光谱和恒温滴定量热法，我们发现黄连素与人端粒四聚体的结合亲和力为10(6)。在25℃时，黄连素与四链体结合的完整热力学曲线显示出一个小的负焓(Delta H)为-1.7kcal.mol(-1)，一个熵变(T Delta S为+6.5kcal.mol(-1))和一个总体有利自由能(Delta G)为-8.2kcal.mol(-1)。通过Delta H的温度依赖关系，我们得到了热容(Delta C-p)为-94(+/-5)cal.mol(-1)·K-1。渗透压力法表明，相对于自由反应物，络合物中有13个水分子被吸收。此外，对不同的四链黄连素络合物的分子模拟研究表明，黄连素在外部G-四重链上的堆积主要是由于pi-pi相互作用和黄连素的正电荷N7稳定鸟嘌呤的高负电荷密度。四联黄连素模型的理论热容(C-p)分别为-89和-156 cal.mol(-1).
This study examines the characteristics of binding of berberine to the human telomeric d[AG(3)(T(2)AG(3))(3)] quadruplex. By employing UV-visible spectroscopy, fluorescence spectroscopy and isothermal titration calorimetry, we found that the binding affinity of berberine to the human telomeric quadruplex is 10(6). The complete thermodynamic profile for berberine binding to the quadruplex, at 25 degrees C, shows a small negative enthalpy (Delta H) of -1.7 kcal.mol(-1), an entropy change with T Delta S of +6.5 kcal.mol(-1), and an overall favorable free energy (Delta G) of -8.2 kcal.mol(-1) .Through the temperature dependence of Delta H, we obtained a heat capacity (Delta C-p) of -94 (+/- 5) cal.mol(-1).K-1. The osmotic stress method revealed that there is an uptake of 13 water molecules in the complex relative to the free reactants. Furthermore, the molecular modeling studies on different quadruplex-berberine complexes show that berberine stacking at the external G-quartet is mainly aided by the pi-pi interaction and the stabilization of the high negative charge density of O6 of guanines by the positively charged N7 of berberine. The theoretical heat capacity (Delta C-p) values for quadruplex-berberine models are -89 and -156 cal.mol(-1).K-1.