Faculty of Chemistry, University of Gdańsk, Wita Stwosza 63, Gdańsk 80-308, Poland.
Department of Chemistry, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, United States.
J Phys Chem B. 2022 Sep 29;126(38):7238-7251. doi: 10.1021/acs.jpcb.2c03138. Epub 2022 Sep 15.
The discovery and introduction of the switchSense technique in the chemical laboratory have drawn well-deserved interest owing to its wide range of applications. Namely, it can be used to determine the diameter of proteins, alterations in their tertiary structures (folding), and many other conformational changes that are important from a biological point of view. The essence of this technique is based on its ability to study of the interactions between an analyte and a ligand in real time (in a buffer flow). Its simplicity, on the other hand, is based on the use of a signaling system that provides information about the ongoing interactions based on the changes in the fluorescence intensity. This technique can be extremely advantageous in the study of new pharmaceuticals. The design of compounds with biological activity, as well as the determination of their molecular targets and modes of interactions, is crucial in the search for new drugs and the fight against drug resistance. This article presents another possible application of the switchSense technique for the study of the binding kinetics of small model molecules such as ethidium bromide (EB) and selected sulfonamide derivatives with DNA in the static and dynamic modes at three different temperatures (15, 25, and 37 °C) each. The experimental results remain in very good agreement with the molecular dynamics docking ones. These physicochemical insights and applications obtained from the switchSense technique allow for the design of an effective strategy for molecular interaction assessments of small but pharmaceutically important molecules with DNA.
开关感应技术在化学实验室中的发现和引入引起了广泛的关注，因为它有广泛的应用。它可以用于测定蛋白质的直径、它们的三级结构（折叠）的变化以及许多其他从生物学角度来看很重要的构象变化。该技术的本质基于其能够实时（在缓冲液流中）研究分析物与配体之间的相互作用。另一方面，其简单性基于使用信号系统，该系统基于荧光强度变化提供关于正在进行的相互作用的信息。这种技术在新药物的研究中非常有利。具有生物活性的化合物的设计，以及它们的分子靶标和相互作用模式的确定，对于寻找新药物和对抗耐药性至关重要。本文提出了开关感应技术的另一种可能的应用，用于研究小模型分子（如溴化乙锭（EB）和选定的磺胺衍生物）与 DNA 的结合动力学，在静态和动态模式下，在三个不同的温度（15、25 和 37°C）下进行。实验结果与分子动力学对接结果非常吻合。从开关感应技术获得的这些物理化学见解和应用允许设计一种有效的策略，用于评估具有生物学重要性的小分子与 DNA 的分子相互作用。
