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白屈菜红碱与双链聚(rA)结合的光谱研究:RNA嵌入模型

Spectroscopic study on the binding of chelerythrine with duplex poly (rA): A model of RNA intercalation.

作者信息

Pradhan Ankur Bikash, Bhuiya Sutanwi, Haque Lucy, Das Suman

机构信息

Department of Chemistry, Jadavpur University, Raja S.C. Mullick Road, Jadavpur, Kolkata 700 032, India.

出版信息

Int J Biol Macromol. 2017 Feb;95:340-347. doi: 10.1016/j.ijbiomac.2016.11.073. Epub 2016 Nov 21.

DOI:10.1016/j.ijbiomac.2016.11.073
PMID:27884672
Abstract

Here we have reported a detail study on the interaction of the benzophenanthridine alkaloid chelerythrine (CHL) with double stranded polyriboadenylic acid [ds poly (rA)] by exploiting various spectroscopic techniques. The alkaloid shows high binding affinity (binding constant is 1.10×10M) towards the double stranded RNA as revealed from Scatchard plot. The binding was confirmed by hypochromic effect in the UV-vis spectrum of CHL, increase in fluorescence intensity of CHL and perturbations of the circular dichroism (CD) spectrum of ds poly (rA). Later fluorescence quenching, cooperative CD melting transition, viscometric and molecular modeling studies establish the fact that the alkaloid binds to the ds poly (rA) by the mechanism of intercalation. Thermodynamic parameters obtained from the isothermal titration calorimetric (ITC) study show that the binding is favoured by negative enthalpy and small positive entropy changes. This report may be a model for intercalation of small molecule like CHL to the double stranded RNA.

摘要

在此,我们通过利用各种光谱技术,报道了关于苯并菲啶生物碱白屈菜红碱(CHL)与双链聚腺苷酸[ds poly (rA)]相互作用的详细研究。从Scatchard图可以看出,该生物碱对双链RNA具有高结合亲和力(结合常数为1.10×10M)。CHL紫外可见光谱中的减色效应、CHL荧光强度的增加以及ds poly (rA)圆二色光谱(CD)的扰动证实了这种结合。随后的荧光猝灭、协同CD熔解转变、粘度测定和分子模拟研究证实了该生物碱通过嵌入机制与ds poly (rA)结合这一事实。等温滴定量热法(ITC)研究获得的热力学参数表明,结合受到负焓变和小的正熵变的促进。本报告可能为像CHL这样的小分子嵌入双链RNA提供一个模型。

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引用本文的文献

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Rediscovery of Traditional Plant Medicine: An Underestimated Anticancer Drug of Chelerythrine.传统植物药的重新发现:白屈菜红碱——一种被低估的抗癌药物
Front Pharmacol. 2022 Jun 1;13:906301. doi: 10.3389/fphar.2022.906301. eCollection 2022.
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Interaction of the putative anticancer alkaloid chelerythrine with nucleic acids: biophysical perspectives.推定的抗癌生物碱白屈菜红碱与核酸的相互作用:生物物理视角
Biophys Rev. 2020 Oct 31;12(6):1369-86. doi: 10.1007/s12551-020-00769-3.