Pawar Suma K, Punith Reeta, Naik Roopa S, Seetharamappa J
a Department of Chemistry , Karnatak University , Dharwad 580003 , India.
J Biomol Struct Dyn. 2017 Nov;35(15):3205-3220. doi: 10.1080/07391102.2016.1251337. Epub 2016 Nov 18.
The interaction between two proton pump inhibitors viz., omeprazole (OME) and esomeprazole (EPZ) with human serum albumin (HSA) was studied by fluorescence, absorption, circular dichroism (CD), Fourier transform infrared spectroscopy (FT-IR), voltammetry, and molecular modeling approaches. The Stern-Volmer quenching constants (K) for OME-HSA and EPZ-HSA systems obtained at different temperatures revealed that both OME and EPZ quenched the intensity of HSA through dynamic mode of quenching mechanism. The binding constants of OME-HSA and EPZ-HSA increased with temperature, indicating the increased stability of these systems at higher temperatures. Thermodynamic parameters viz., ∆H, ∆S, and ∆G were determined for both systems. These values revealed that both systems were stabilized by hydrophobic forces. The competitive displacement and molecular docking studies suggested that OME/EPZ was bound to Sudlow's site I in subdomain IIA in HSA. The extent of energy transfer from HSA to OME/EPZ and the distance of separation in tryptophan (Trp214) Trp214-OME and Trp214-EPZ was determined based on the theory of fluorescence resonance energy transfer. UV absorption, 3D fluorescence, and CD studies indicated that the binding of OME/EPZ to HSA has induced micro environmental changes around the protein which resulted changes in its secondary structure.
采用荧光、吸收、圆二色性（CD）、傅里叶变换红外光谱（FT-IR）、伏安法和分子模拟方法研究了两种质子泵抑制剂即奥美拉唑（OME）和埃索美拉唑（EPZ）与人血清白蛋白（HSA）之间的相互作用。在不同温度下获得的OME-HSA和EPZ-HSA体系的斯特恩-沃尔默猝灭常数（K）表明，OME和EPZ均通过动态猝灭机制猝灭了HSA的荧光强度。OME-HSA和EPZ-HSA的结合常数随温度升高而增加，表明这些体系在较高温度下稳定性增强。测定了两个体系的热力学参数，即∆H、∆S和∆G。这些值表明两个体系均通过疏水力得以稳定。竞争性置换和分子对接研究表明，OME/EPZ与HSA亚结构域IIA中的Sudlow位点I结合。基于荧光共振能量转移理论，测定了从HSA到OME/EPZ的能量转移程度以及色氨酸（Trp214）与Trp214-OME和Trp214-EPZ之间的距离。紫外吸收、三维荧光和CD研究表明，OME/EPZ与HSA的结合诱导了蛋白质周围的微环境变化，从而导致其二级结构发生改变。
