应用分子对接和光谱方法研究雷戈非尼与人血清白蛋白（HSA）和小牛胸腺 DNA（Ct-DNA）在不同位点标记存在下的相互作用。
The Use of Molecular Docking and Spectroscopic Methods for Investigation of The Interaction Between Regorafenib with Human Serum Albumin (HSA) and Calf Thymus DNA (Ct-DNA) In The Presence Of Different Site Markers.
机构信息
Research Center for Molecular Medicine, Hamadan University of Medical Sciences, Hamadan, Iran.
Vascular and Endovascular Surgery Research Centre, Mashhad University of Medical Sciences, Mashhad, Iran.
出版信息
Protein Pept Lett. 2021;28(3):290-303. doi: 10.2174/0929866527666200921164536.
BACKGROUND
Interactions of drugs with DNA and proteins may modify their biological activities and conformations, which effect transport and biological metabolism of drugs.
OBJECTIVE
In this study the interaction of anticancer drug regorafenib (REG) with calf thymus-DNA (ct-DNA) and human serum albumin (HSA) has been investigated Methods: Hence, for the first time, it was discovered interaction between REG with DNA and HSA using multi-spectroscopic, zeta potential measurements and molecular docking method.
RESULTS AND DISCUSSION
DNA displacement studies showed that REG does not have any effect on acridine orange and methylene blue bound DNA, though it was substantiated by displacement studies with Hoechst (as groove binder). Furthermore, the different concentrations of REG induce slight changes in the viscosity of ct-DNA. Zeta potential parameters indicated that hydrophobic interaction plays a major role in the DNA-REG complex. Results obtained from molecular docking demonstrate that the REG prefers to bind on the minor groove of DNAs than that of the major groove. Binding properties of HSA reveal that intrinsic fluorescence of HSA could be quenched by REG in a static mode. The competitive experiments in the presence of warfarin and ibuprofen (as site markers) suggested that the binding site of REG to HSA was most probably located in the subdomain IIA. Measurements of the zeta potential indicated that REG bound to HSA mainly by both electrostatic and hydrophobic interactions. It was found on docking procedures that REG could fit well into HSA subdomain IIA, which confirmed the experimental results.
CONCLUSION
In conclusion, REG can be delivered by HSA in a circulatory system and affect DNA as potential target.
背景
药物与 DNA 和蛋白质的相互作用可能会改变它们的生物活性和构象，从而影响药物的运输和生物代谢。
目的
本研究考察了抗癌药物regorafenib（REG）与小牛胸腺 DNA（ct-DNA）和人血清白蛋白（HSA）的相互作用。
方法
因此，首次采用多光谱、Zeta 电位测量和分子对接方法发现了 REG 与 DNA 和 HSA 的相互作用。
结果与讨论
DNA 置换研究表明，REG 对吖啶橙和亚甲基蓝结合的 DNA 没有任何影响，尽管用 Hoechst（作为沟结合剂）进行置换研究证实了这一点。此外，不同浓度的 REG 会引起 ct-DNA 粘度的轻微变化。Zeta 电位参数表明，疏水相互作用在 DNA-REG 复合物中起主要作用。分子对接结果表明，REG 更倾向于结合 DNA 的小沟，而不是大沟。HSA 的结合特性表明，REG 可以以静态模式猝灭 HSA 的固有荧光。在华法林和布洛芬（作为位点标记物）存在的竞争实验中，表明 REG 与 HSA 的结合位点很可能位于亚域 IIA。Zeta 电位测量表明，REG 主要通过静电和疏水相互作用与 HSA 结合。在对接程序中发现，REG 可以很好地适应 HSA 的亚域 IIA，这证实了实验结果。
结论
总之，REG 可以通过 HSA 在循环系统中输送，并作为潜在的靶标影响 DNA。
Zotero 插件