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Enhancement Effect of Zn-Arsenazo III Complex for G-quadruplex DNA Stability of Proto-oncogene Promoter Telomeres
Letters in Drug Design & Discovery ( IF 1 ) Pub Date : 2020-05-31 , DOI: 10.2174/1570180816666191112154141
Liyuan Zou 1 , Hongbo Li 1 , Mingbin Liu 1 , Weihua Zhao 1 , Suqin Wang 1
Affiliation  

Background: Controlling the structure of proto-oncogene telomeres is very important in antitumor therapy. There are relationships between G-quadruplex DNA and the growth of tumor cell.

Methods: In this study, spectroscopic, cyclic voltammetry and viscosity methods were employed to investigate the interaction between Zn-Arsenazo Ⅲ complex and G-quadruplex DNA by using 4S Green Plus Nucleic Acid Stain as a spectral probe in PBS buffer. The binding ratios were n Arsenazo Ⅲ : n Zn(Ⅱ) = 5:1 for Zn-Arsenazo Ⅲ complex and n Zn- Arsenazo Ⅲ : n G-quadruplex DNA = 8:1 for Zn-Arsenazo Ⅲ-G-quadruplex DNA. The bonding constants (Kθ 298.15K=4.44x105 L·mol-1, Kθ 308.15K= 1.00x105 L·mol-1, Kθ 318.15K= 1.04x106 L·mol-1) were obtained by double reciprocal method at different temperatures, Which was found that the interaction between Zn-Arsenazo Ⅲ complex and Gquadruplex DNA was driven by enthalpy. Furthermore, the research further confirmed that the interaction mode between Zn-Arsenazo Ⅲ complex and G-quadruplex DNA was a mixed binding which involved intercalation and non-intercalation interaction.

Results and Conclusion: Together these findings also have corroborated the application of stabilizing ligands and intervening with their function for target G-quadruplexes in a cellular context.



中文翻译:

锌-砷偶氮III配合物对原癌基因启动子端粒G-四链体DNA稳定性的增强作用

背景:控制原癌基因端粒的结构在抗肿瘤治疗中非常重要。G-四链体DNA与肿瘤细胞的生长之间存在联系。

方法:采用光谱,循环伏安法和粘度法,以PBS缓冲液中的4S Green Plus核酸染色剂为探针,研究Zn-ArsenazoⅢ配合物与G-quadruplex DNA之间的相互作用。Zn-ArsenazoⅢ复合物的结合比为n ArsenazoⅢ:n Zn(Ⅱ)= 5:1,而Zn-ArsenazoⅢ-G-quadruplexDNA的n Zn- ArsenazoⅢ:n G-quadruplex DNA = 8:1。接合常数(Kθ 298.15K = 4.44x10 5 L·摩尔-1,Kθ 308.15K = 1.00×10 5 L·摩尔-1,Kθ 318.15K = 1.04x10 6 L·摩尔-1)是在不同温度下通过双向倒数法获得的,结果发现Zn-ArsenazoⅢ复合物与Gquadruplex DNA之间的相互作用是由焓驱动的。此外,研究进一步证实Zn-ArsenazoⅢ复合物与G-四链体DNA之间的相互作用方式是混合结合,涉及嵌入和非嵌入相互作用。

结果与结论:这些发现共同也证实了稳定配体的应用及其在细胞环境中对靶G-四链体的功能干预。

更新日期:2020-05-31
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