Department of Chemistry, Karnatak University, Dharwad 580 003, India.
Spectrochim Acta A Mol Biomol Spectrosc. 2012 Feb;86:410-6. doi: 10.1016/j.saa.2011.10.060. Epub 2011 Nov 7.
The mechanism of interaction of ondansetron hydrochloride (OND) to serum albumins [bovine serum albumin (BSA) and human serum albumin (HSA)] was studied for the first time employing fluorimetric, circular dichroism, FTIR and UV-vis absorption techniques under the simulated physiological conditions. Fluorimetric results were utilized to investigate the binding and conformational characteristics of protein upon interaction with varying concentrations of the drug. Higher binding constant values revealed the strong interaction between the drug and protein while the number of binding sites close to unity indicated single class of binding site for OND in protein. Thermodynamic results revealed that both hydrogen bond and hydrophobic interactions played a major role in stabilizing drug-protein complex. Site marker competitive experiments indicated that the OND bound to albumins at subdomin II A (Sudlow's site I). Further, the binding distance between OND and serum albumin was calculated based on the Förster's theory of non-radioactive energy transfer and found to be 2.30 and 3.41 nm, respectively for OND-BSA and OND-HSA. The circular dichroism data revealed that the presence of OND decreased the α-helix content of serum albumins. 3D-fluorescence results also indicated the conformational changes in protein upon interaction with OND. Further, the effects of some cations have been investigated in the interaction of drug to protein.
首次在模拟生理条件下，运用荧光、圆二色性、FTIR 和紫外可见吸收技术研究了盐酸昂丹司琼（OND）与血清白蛋白（牛血清白蛋白（BSA）和人血清白蛋白（HSA））相互作用的机制。荧光结果用于研究药物浓度变化时蛋白质相互作用的结合和构象特征。较高的结合常数值表明药物与蛋白质之间存在强烈相互作用，而结合位点数接近 1 表明 OND 在蛋白质中有单一位点结合。热力学结果表明，氢键和疏水相互作用在稳定药物-蛋白质复合物中起主要作用。位点标记竞争实验表明，OND 结合在白蛋白的亚域 II A（Sudlow 位点 I）上。此外，根据福斯特非放射性能量转移理论，计算了 OND 与血清白蛋白之间的结合距离，分别为 OND-BSA 和 OND-HSA 的 2.30nm 和 3.41nm。圆二色性数据表明，OND 的存在降低了血清白蛋白的α-螺旋含量。3D-荧光结果也表明了 OND 与蛋白质相互作用时蛋白质构象的变化。此外，还研究了一些阳离子对药物与蛋白质相互作用的影响。
