Department of Chemistry, Karunya Institute of Technology and Sciences (Deemed-to-be University), Coimbatore, Tamil Nadu, India.
Centre for Nanoscience and Genomics, Karunya Institute of Technology and Sciences (Deemed-to-be University), Coimbatore, Tamil Nadu, India.
J Biomol Struct Dyn. 2023 Jun;41(9):3791-3799. doi: 10.1080/07391102.2022.2056508. Epub 2022 Apr 1.
Clinical applicability of G-quadruplexes as anticancer drugs is an area of current interest. Identification of supramolecular systems for selective targeting G-quartets is particularly intriguing. In this work, the DNA binder Berberine is encapsulated inside the molecular cavity of the synthesised host structure, Fluoresecein-β-cyclodextrin conjugate. The host: guest complex is characterized and the mode of binding is optimized using two dimensional rotating-frame Overhauser effect spectroscopy. The conjugate is examined for its binding to quadruplex DNAs viz., , and the duplex calf-thymus DNA before and after Berberine encapsulation. UV-vis and fluorescence spectroscopic methods were employed to determine the strength of binding of the complex with the DNAs. The binding strength and the stoichiometry of the host: guest complex are 1.9×10mol dm and 1:1, respectively. A quenching of fluorescence of the quadruplex and duplex ctDNA is observed on binding to the Fluorescein-β-cyclodextrin conjugate. The quadruplexes of and display an enhanced fluorescence on binding to the modified cyclodextrin. The Stern-Volmer quenching constants are 1.4×10mol dm and 3.8×10mol dm for binding to and ctDNA respectively. shows a different emission profile on interacting with the Berberine encapsulated conjugate, whereas all the other quadruplexes and duplex exhibit similar emission profiles. The results indicate a variation in the binding mode and strength of the ligand-quadruplexes and depend on the conformation of the quadruplexes.Communicated by Ramaswamy H. Sarma.
G-四链体作为抗癌药物的临床适用性是当前的研究热点。识别选择性靶向 G-四联体的超分子体系特别有趣。在这项工作中，将 DNA 结合剂小檗碱包封在合成主体结构荧光素-β-环糊精缀合物的分子腔内。对主体-客体配合物进行了表征，并通过二维旋转框架 Overhauser 效应光谱优化了结合方式。研究了该缀合物与四链体 DNA（即 、 、 ）和双链小牛胸腺 DNA 的结合情况，以及包封小檗碱前后的结合情况。采用紫外-可见光谱和荧光光谱法测定了配合物与 DNA 的结合强度。该配合物与 DNA 的结合强度和化学计量比分别为 1.9×10mol dm 和 1:1。结合到荧光素-β-环糊精缀合物上时，观察到四链体 和双链 ctDNA 的荧光猝灭。与修饰后的环糊精结合时， 和 的四链体显示出增强的荧光。与 ctDNA 结合的 Stern-Volmer 猝灭常数分别为 1.4×10mol dm 和 3.8×10mol dm。 与包封小檗碱的缀合物相互作用时呈现出不同的发射谱，而其他所有四链体和双链体都表现出相似的发射谱。结果表明，配体-四链体的结合方式和强度存在差异，这取决于四链体的构象。由 Ramaswamy H. Sarma 传达。
