Khamari Laxmikanta, Mukherjee Saptarshi
Department of Chemistry, Indian Institute of Science Education and Research Bhopal, Bhopal Bypass Road, Bhauri, Bhopal 462 066, Madhya Pradesh, India.
J Phys Chem Lett. 2022 Sep 1;13(34):8169-8176. doi: 10.1021/acs.jpclett.2c01893. Epub 2022 Aug 25.
Intercalated-motif (i-motif) DNA formed by cytosine (C)-rich sequences has been considered a novel target in anticancer research. Interestingly, this type of noncanonical DNA structure is highly dynamic and can display several conformational polymorphisms based on the immediate surrounding environment. However, studies regarding the folding pathway of i-motifs having disease-specific sequences under a confined environment at physiological pH are relatively scarce. This thereby warrants more explorations that will decipher their structural and functional properties inside constrained media. Herein, using the single-molecule Förster Resonance Energy Transfer (smFRET) studies, for the first time, we have illustrated the conformational dynamics of promoter-based i-motif structures at physiological pH inside microemulsions of different dimensions. We concluded that the folding of such motifs under confined space is not a direct transition between the random coil and i-motif conformations; rather it occurs through a partially folded intermediate, depending on the confined dimension.
由富含胞嘧啶（C）的序列形成的插入基序（i-基序）DNA已被视为抗癌研究中的一个新靶点。有趣的是，这种非经典DNA结构具有高度动态性，并且可以根据周围环境呈现多种构象多态性。然而，关于在生理pH值的受限环境下具有疾病特异性序列的i-基序折叠途径的研究相对较少。因此，这需要更多的探索来解读它们在受限介质中的结构和功能特性。在此，我们首次使用单分子荧光共振能量转移（smFRET）研究，阐明了在不同尺寸微乳液中生理pH值下基于启动子的i-基序结构的构象动力学。我们得出结论，这种基序在受限空间中的折叠不是随机线圈和i-基序构象之间的直接转变；相反，它通过一个部分折叠的中间体发生，这取决于受限尺寸。
