Department of Analytical Chemistry, Faculty of Pharmacy, Ankara University, Ankara 06560, Turkey.
The Graduate School of Health Sciences, Ankara University, Ankara 06110, Turkey.
Biosensors (Basel). 2022 Apr 27;12(5):278. doi: 10.3390/bios12050278.
The binding of drugs to DNA plays a critical role in new drug discovery and is important for designing better drugs. In this study, the interaction and binding mode of calf-thymus double-stranded deoxyribonucleic acid (ct-dsDNA) with cinacalcet (CIN) from the calcimimetic drug that mimics the action of calcium on tissues group were investigated. The interaction of CIN with ct-dsDNA was observed by the differential pulse voltammetry (DPV) technique by following the decrease in electrochemical oxidation signals to deoxyguanosine and adenosine. A competitive study was performed on an indicator, methylene blue, to investigate the interaction of the drug with ct-dsDNA by fluorescence spectroscopy. Interaction studies have shown that the binding mode for the interaction of CIN with ct-dsDNA could be groove-binding. According to the results obtained, the binding constant values were found to be 6.30 × 10 M and 3.16 × 10 M, respectively, at 25 °C as obtained from the cyclic voltammetry (CV) and spectroscopic techniques. Possible molecular interactions of CIN with dsDNA were explored via molecular docking experiments. The docked structure indicated that CIN could fit well into the minor groove of the DNA through H-bonding and π-π stacking contact with CIN.
药物与 DNA 的结合在新药发现中起着至关重要的作用，对于设计更好的药物也很重要。在这项研究中，研究了模拟钙对组织作用的拟钙剂药物中钙三醇（CIN）与小牛胸腺双链脱氧核糖核酸（ct-dsDNA）的相互作用和结合模式。通过示踪脱氧鸟苷和腺嘌呤电化学氧化信号的降低，使用差分脉冲伏安法（DPV）技术观察 CIN 与 ct-dsDNA 的相互作用。通过荧光光谱法进行竞争性研究，以研究药物与 ct-dsDNA 的相互作用。相互作用研究表明，CIN 与 ct-dsDNA 的相互作用结合模式可能是沟槽结合。根据循环伏安法（CV）和光谱技术获得的结果，在 25°C 时，CIN 与 ct-dsDNA 的结合常数值分别为 6.30×10^M 和 3.16×10^M。通过分子对接实验探索了 CIN 与 dsDNA 的可能分子相互作用。对接结构表明，CIN 可以通过氢键和 CIN 与 DNA 之间的π-π堆积接触，很好地适应 DNA 的小沟。
