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Probing the Strength and Mechanism of Binding Between Amifampridine and Calf Thymus DNA

机译:促进阿米米嘌呤和小牛胸腺DNA结合的强度和机制

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In this work, we have investigated the strength and mechanism of amifampridine (3,4-Diaminopyridine/3,4-DAP) interaction with calf thymus DNA (ct-DNA). The existence and the strength of interaction are evaluated using circular dichroism (CD), UV-vis absorption, and differential pulse voltammogram studies. Results from UV-vis absorption technique indicate that amifampridine can significantly interact with DNA through a binding constant ofK(b) = 1.66 x 10(5)M(-1)at 298 K. The mechanism of the interaction between amifampridine and DNA is also studied using ionic effect investigations, competitive fluorescence experiments, viscosity measurements, and molecular docking studies. The viscosity results indicate that amifampridine can bind to DNA via intercalation binding mode. Competitive fluorescence experiments using Acridine Orange (AO) and Hoechst 33258 (HO) probes also reveal that amifampridine binds to DNA via an intercalation mode of binding. Finally, the molecular docking studies also suggest that amifampridine tends to bind with the G-C rich region of DNA.
机译:在这项工作中,我们研究了阿米法普利定(3,4-二氨基吡啶/3,4-DAP)与小牛胸腺DNA(ct DNA)相互作用的强度和机制。利用圆二色性(CD)、紫外-可见吸收和差分脉冲伏安法研究了相互作用的存在和强度。紫外-可见吸收技术的结果表明,在298K下,阿米法普利定可以通过K(b)=1.66 x 10(5)M(-1)的结合常数与DNA发生显著的相互作用。还利用离子效应研究、竞争荧光实验、粘度测量和分子对接研究了阿米法普利定与DNA的相互作用机制。粘度结果表明,阿米法普利定可以通过插层结合方式与DNA结合。使用吖啶橙(AO)和Hoechst 33258(HO)探针进行的竞争性荧光实验也表明,阿米法普利定通过嵌入结合模式与DNA结合。最后,分子对接研究还表明阿米法普利定倾向于与DNA富含G-C的区域结合。

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