Sadia Nudrat, Bilash Maity, Sana Quraishi, Irungbam Karankumar, Kalpana Kumari, Madhurima Jana, Atanu Singha Roy
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Interestingly, circular dichroism and Fourier transform infrared studies showed a significant change in the secondary structure of OVA upon binding with daphnetin. The efficacy of daphnetin in inhibiting protein fibrillation was confirmed through thioflavin T and Congo Red binding assays along with fluorescence microscopic imaging analysis. The thermodynamic assessment showed positive Δ<i>H</i>° [+(29.34 ± 1.526) kJ mol<sup>-1</sup>] and Δ<i>S</i>° [+(181.726 ± 5.465) J mol<sup>-1</sup>] values, indicating the presence of the hydrophobic forces, while negative Δ<i>G</i>° signifies spontaneous binding interactions. 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引用次数: 0
摘要
本研究利用光谱和计算分析方法研究了水飞萘素与卵清蛋白(OVA)之间的相互作用及其抑制 OVA 纤维化的潜力。在荧光淬灭过程中,发现 OVA 与水飞萘素之间的结合亲和力为 1 × 104 M-1,属于中等程度的静态淬灭机制。金属离子(Cu2+ 和 Zn2+)的存在增加了水黄素与 OVA 的结合亲和力,这与 pH 值的变化趋势相似。同步和三维荧光研究表明,在结合过程中,Trp 残基周围微环境的极性增加。有趣的是,圆二色性和傅立叶变换红外研究表明,OVA 与水飞萘素结合后,其二级结构发生了显著变化。通过硫黄素 T 和刚果红结合试验以及荧光显微成像分析,证实了萘素在抑制蛋白质纤维化方面的功效。热力学评估显示,ΔH° [+(29.34 ± 1.526) kJ mol-1] 和 ΔS° [+(181.726 ± 5.465) J mol-1] 值为正,表明存在疏水力,而ΔG° 为负,表明存在自发的结合相互作用。这些实验结果与计算分析进一步相关联,揭示了 OVA 结合位点内水苏碱的动态变化。
Binding Interaction of Coumarin Derivative Daphnetin with Ovalbumin: Molecular Insights into the Complexation Process and Effects of Metal Ions and pH in the Binding and Antifibrillation Studies.
This study investigates the interaction between daphnetin and ovalbumin (OVA) as well as its potential to inhibit OVA fibrillation using both spectroscopic and computational analysis. A moderate binding affinity of 1 × 104 M-1 was observed between OVA and daphnetin, with a static quenched mechanism identified during the fluorescence quenching processes. Metal ions' (Cu2+ and Zn2+) presence led to an increase in the binding affinities of daphnetin toward OVA, mirroring a similar trend observed with the pH variation. Synchronous and 3D fluorescence studies indicated an increase in the polarity of the microenvironment surrounding the Trp residues during binding. Interestingly, circular dichroism and Fourier transform infrared studies showed a significant change in the secondary structure of OVA upon binding with daphnetin. The efficacy of daphnetin in inhibiting protein fibrillation was confirmed through thioflavin T and Congo Red binding assays along with fluorescence microscopic imaging analysis. The thermodynamic assessment showed positive ΔH° [+(29.34 ± 1.526) kJ mol-1] and ΔS° [+(181.726 ± 5.465) J mol-1] values, indicating the presence of the hydrophobic forces, while negative ΔG° signifies spontaneous binding interactions. These experimental findings were further correlated with computational analysis, revealing daphnetin dynamics within the binding site of OVA.
期刊介绍:
Molecular Pharmaceutics publishes the results of original research that contributes significantly to the molecular mechanistic understanding of drug delivery and drug delivery systems. The journal encourages contributions describing research at the interface of drug discovery and drug development.
Scientific areas within the scope of the journal include physical and pharmaceutical chemistry, biochemistry and biophysics, molecular and cellular biology, and polymer and materials science as they relate to drug and drug delivery system efficacy. Mechanistic Drug Delivery and Drug Targeting research on modulating activity and efficacy of a drug or drug product is within the scope of Molecular Pharmaceutics. Theoretical and experimental peer-reviewed research articles, communications, reviews, and perspectives are welcomed.