Deciphering the interaction of perampanel and calf thymus DNA: A multi-spectroscopic and computer modelling study

IF 4 2区化学 Q2 CHEMISTRY, PHYSICAL Journal of Molecular Structure Pub Date : 2022-12-15 DOI:10.1016/j.molstruc.2022.133900

Yating Lei , Zihang Zhang , Xiulan Ma , Ruirui Cai , Lulu Dai , Ying Guo , Xun Tuo

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引用次数: 1

Abstract

Perampanel (PER) is the first drug to treat epilepsy by blocking α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors. In the current study, the interaction of PER and calf thymus DNA (ctDNA) was explored through various spectroscopic techniques and computer modelling. According to the UV-vis titration results, PER combined with ctDNA via groove binding, which was also confirmed by thermal melting, salt effect, ssDNA/dsDNA quenching, and competitive experiments. The dominant forces were hydrogen bond and van der Waals force. And the binding constant obtained was 6.97 × 10³ M⁻¹ at 298 K. According to the data from FTIR assays and computer modelling, PER was embedded in the minor groove of ctDNA rich in A and T bases. In the simulation of 200 ns, the PER-DNA system reached equilibrium at about 100 ns. The structure of DNA became loose when a stable binary complex with PER was formed. The energy decomposition indicated that DC-9, DT-19, and DT-20 bases played a main role in this complex-forming. In summary, this study contributed to understanding the interaction mechanism of PER and ctDNA.

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解读perampanel和小牛胸腺DNA的相互作用:一项多光谱和计算机建模研究

Perampanel (PER)是首个通过阻断α-氨基-3-羟基-5-甲基-4-异恶唑丙酸受体治疗癫痫的药物。在目前的研究中，通过各种光谱技术和计算机建模来探索PER和小牛胸腺DNA (ctDNA)的相互作用。根据UV-vis滴定结果，PER通过槽结合与ctDNA结合，并通过热熔融、盐效应、ssDNA/dsDNA猝灭和竞争实验证实了这一点。主要的作用力是氢键力和范德华力。在298 K下得到的结合常数为6.97 × 103 M−1。根据FTIR分析和计算机模拟的数据，PER嵌入在富含A和T碱基的ctDNA的小凹槽中。在200 ns的模拟中，PER-DNA系统在100 ns左右达到平衡。当与PER形成稳定的二元配合物时，DNA的结构变得松散。能量分解表明，DC-9、DT-19和DT-20碱基在络合物形成中起主要作用。综上所述，本研究有助于理解PER与ctDNA的相互作用机制。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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文献相关原料

公司名称	产品信息	采购帮参考价格
上海源叶	Bisbenzimide H33258 Fluorochrome (H33258)	￥46.00~￥26817.00
阿拉丁	Perampanel	￥127.00~￥25620.00
上海源叶	Ethidium bromide (EB)	￥27.00~￥7650.00

来源期刊

Journal of Molecular Structure 化学-物理化学

CiteScore

7.10

自引率

15.80%

发文量

2384

审稿时长

45 days

期刊介绍： The Journal of Molecular Structure is dedicated to the publication of full-length articles and review papers, providing important new structural information on all types of chemical species including: • Stable and unstable molecules in all types of environments (vapour, molecular beam, liquid, solution, liquid crystal, solid state, matrix-isolated, surface-absorbed etc.) • Chemical intermediates • Molecules in excited states • Biological molecules • Polymers. The methods used may include any combination of spectroscopic and non-spectroscopic techniques, for example: • Infrared spectroscopy (mid, far, near) • Raman spectroscopy and non-linear Raman methods (CARS, etc.) • Electronic absorption spectroscopy • Optical rotatory dispersion and circular dichroism • Fluorescence and phosphorescence techniques • Electron spectroscopies (PES, XPS), EXAFS, etc. • Microwave spectroscopy • Electron diffraction • NMR and ESR spectroscopies • Mössbauer spectroscopy • X-ray crystallography • Charge Density Analyses • Computational Studies (supplementing experimental methods) We encourage publications combining theoretical and experimental approaches. The structural insights gained by the studies should be correlated with the properties, activity and/ or reactivity of the molecule under investigation and the relevance of this molecule and its implications should be discussed.