Department of Biochemistry, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran.
Department of Cell & Molecular Sciences, Faculty of Biological Sciences, Kharazmi University, Tehran, Iran.
J Biomol Struct Dyn. 2021 Feb;39(3):1004-1016. doi: 10.1080/07391102.2020.1733091. Epub 2020 Mar 5.
In the present study, the simultaneous carrier ability of natural antioxidant of astaxanthin (ATX) and chemotherapeutic drug of 5-fluorouracil (5-FU) by whey protein of β-lactoglobulin (β-LG) using various spectroscopic techniques (UV-visible, fluorescence, circular dichroism (CD) and dynamic light scattering) in combination with molecular docking were investigated (at room and physiological temperatures). According to the fluorescence quenching tests, the binding parameters between drug and ATX with protein showed that the number of their binding sites was the same in the single and competitive states. Molecular docking results have showed completely consistent with the fluorescence data that presented the independent binding sites for 5-FU and ATX on β-LG. Also, analysis of Far-UV-CD showed that the simultaneous binding of the drugs to the protein partially enhances its stability, which is associated with the decreasing in β-sheet structure and increasing in α-helix. According to the Zeta potential measurements in the presence of different concentrations of the drugs, they have stronger binding to the protein at lower concentrations. Therefore, given the remarkable features of β-LG, including the ability to interact simultaneously with the natural compound of ATX and the antitumor drug of 5-FU, this study could provide useful information for the development and improvement of new protein carrier systems with synergism potency. Communicated by Ramaswamy H. Sarma.
在本研究中,使用各种光谱技术(紫外-可见、荧光、圆二色性(CD)和动态光散射)结合分子对接研究了乳清蛋白β-乳球蛋白(β-LG)对天然抗氧化剂虾青素(ATX)和化疗药物 5-氟尿嘧啶(5-FU)的同时载体能力(在室温及生理温度下)。根据荧光猝灭实验,药物与 ATX 与蛋白质的结合参数表明,在单态和竞争态下,它们的结合位点数量相同。分子对接结果与荧光数据完全一致,表明 5-FU 和 ATX 在β-LG 上具有独立的结合位点。此外,远紫外 CD 分析表明,药物同时结合到蛋白质上会部分增强其稳定性,这与β-折叠结构的减少和α-螺旋的增加有关。根据存在不同药物浓度时的 Zeta 电位测量结果,它们在较低浓度下与蛋白质具有更强的结合能力。因此,鉴于 β-LG 的显著特性,包括与天然化合物 ATX 和抗肿瘤药物 5-FU 同时相互作用的能力,本研究可为开发和改进具有协同作用潜力的新型蛋白质载体系统提供有用信息。由 Ramaswamy H. Sarma 传达。