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Sodium valproate (VPA) interactions with DNA and histones.
International Journal of Biological Macromolecules ( IF 7.7 ) Pub Date : 2020-06-30 , DOI: 10.1016/j.ijbiomac.2020.06.265
Benedicto de Campos Vidal 1 , Maria Luiza S Mello 1
Affiliation  

Valproic acid/sodium valproate (VPA) constitutes a widely prescribed drug for the treatment of seizure disorders and is a well-known epigenetic agent, inducing the acetylation of histones and affecting the methylation status of DNA and histones, with consequences on gene expression. Because this drug has been recently reported to exert affinity for histone H1, and to a minor degree for DNA, in this work, we investigated a possible interaction of sodium valproate with DNA and histones H1 and H3 using high-performance polarization microscopy and Fourier-transform infrared (FTIR) microspectroscopy. The preparations under examination consisted of hemispheres resulting from drop-casting samples containing VPA-DNA and VPA-histone mixtures. The results indicated that VPA may interact with DNA and histones, inducing changes in the textural superstructure and molecular order of the DNA possibly through van der Waals forces, and in histone H1 and H3 conformations, probably as a result of electrostatic binding between the drug and protein amino acid residues. These results contribute to a better understanding of the pharmacological potential of VPA. The precise sites and mechanisms involved in these interactions would certainly benefit from investigations provided by complementary methodologies.



中文翻译:

丙戊酸钠(VPA)与DNA和组蛋白的相互作用。

丙戊酸/丙戊酸钠(VPA)是治疗癫痫病的一种广泛处方药物,并且是众所周知的表观遗传药物,可诱导组蛋白的乙酰化并影响DNA和组蛋白的甲基化状态,从而影响基因表达。由于最近有报道称该药对组蛋白H1具有亲和力,并且对DNA的亲和力较小,因此在这项工作中,我们使用高效能偏振显微镜和傅里叶-变换红外(FTIR)显微光谱。被检查的制剂由含有VPA-DNA和VPA-组蛋白混合物的滴铸样品得到的半球组成。结果表明VPA可能与DNA和组蛋白相互作用,可能通过范德华力以及组蛋白H1和H3构象诱导DNA的结构上层结构和分子顺序的变化,这可能是药物与蛋白质氨基酸残基之间静电结合的结果。这些结果有助于更好地了解VPA的药理潜力。这些相互作用中涉及的确切位置和机制必将受益于补充方法学提供的研究。

更新日期:2020-07-07
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