Department of Chemistry, Gandhigram Rural Institute (Deemed to be University), Gandhigram 624 302, India.
Department of Chemistry, Gandhigram Rural Institute (Deemed to be University), Gandhigram 624 302, India.
Spectrochim Acta A Mol Biomol Spectrosc. 2022 Oct 5;278:121363. doi: 10.1016/j.saa.2022.121363. Epub 2022 May 10.
Remdesivir (REM) is an antiviral drug, which exercises its effect by targeting specifically RNA-dependent RNA polymerase. The interaction of REM with calf thymus DNA (CT-DNA) was investigated by multi-spectroscopic techniques (UV-Vis, fluorescence, circular dichroism and P NMR) in combination with different biophysical experiments and metadynamics simulation studies. UV-Vis and fluorescence spectroscopic analysis indicated formation of a complex between REM and CT-DNA, whose binding constant is in the order of 10 M. Competitive displacement assays with ethidium bromide (EB) and Hoechst 33258 shown that REM binds to CT-DNA via intercalation mode. Significant alteration in the band due to base stacking pairs at 274 nm in the circular dichroism spectrum, appreciable increase in relative viscosity of the biomolecule upon binding with REM and the results of potassium iodide quenching studies confirmed that REM intercalates into the base pairs of CT-DNA. Thermodynamic parameters revealed that the binding of REM to CT-DNA is a spontaneous process (ΔG < 0) and the main force which holds them together in the REM/CT-DNA complex is electrostatic interaction (ΔH < 0 and ΔS > 0). The up-field shift in the P NMR signal of REM on interaction with CT-DNA suggested that phenyl ring adjacent to the phosphate moiety of REM may involve in the intercalation process. This is well supported by the analysis of free energy surface landscape derived from metadynamics simulation studies.
瑞德西韦（REM）是一种抗病毒药物，通过靶向 RNA 依赖性 RNA 聚合酶来发挥作用。采用多种光谱技术（UV-Vis、荧光、圆二色性和 P NMR）结合不同的生物物理实验和元动力学模拟研究，研究了 REM 与小牛胸腺 DNA（CT-DNA）的相互作用。UV-Vis 和荧光光谱分析表明，REM 与 CT-DNA 形成复合物，其结合常数为 10 M 级。与溴化乙锭（EB）和 Hoechst 33258 的竞争性置换实验表明，REM 通过嵌入模式与 CT-DNA 结合。圆二色性光谱中 274nm 处由于碱基堆积对引起的谱带明显改变，与 REM 结合后生物分子的相对粘度显著增加，以及碘化钾猝灭研究的结果证实 REM 嵌入 CT-DNA 的碱基对中。热力学参数表明，REM 与 CT-DNA 的结合是一个自发过程（ΔG<0），将它们结合在一起的主要力是静电相互作用（ΔH<0 和 ΔS>0）。与 CT-DNA 相互作用时 REM 的 P NMR 信号的向上场位移表明，REM 磷酸部分附近的芳环可能参与嵌入过程。这得到了元动力学模拟研究得出的自由能表面景观分析的很好支持。
