Guangzhou Key Laboratory of Insect Development Regulation and Application Research, Institute of Insect Science and Technology, School of Life Sciences, South China Normal University, Guangzhou, 510631, China.
School of Pharmacy, Peking University, Beijing, 100191, China.
Biochem Biophys Res Commun. 2022 Jan 22;589:9-15. doi: 10.1016/j.bbrc.2021.11.092. Epub 2021 Nov 27.
DNA secondary structure i-motif involves in gene transcription and considered as a novel target for cancer gene therapy. I-motif-binding compounds can either stabilize or destroy the structure, resulting in change in target gene transcription. In this study, a large-scale screening of binding compounds was conducted using the i-motif structure of BmPOUM2, a transcription factor in silkworm, Bombyx mori. Surface plasmon resonance imaging (SPRi) high-throughput binding screening of 3642 compounds found 60 compounds with an binding affinity K of 10-10 M. SPRi and circular dichroism (CD) double screening demonstrated that the BmPOUM2 i-motif structure bound the compounds IF1, IF3, IF4, IF6 and IF7 with K of 10 M, and the compounds IF2 and tetrakis (4-N-methylpyridyl) porphine (TMPyP4) with a K of 10 M. Interestingly, IF2, IF3, IF4, IF6 and IF7 promoted the binding of the i-motif-binding protein BmILF with the i-motif structure, whereas TMPyP4 inhibited the binding. This study provided a list of compounds that have potential applications in functional analysis of i-motif structure and in pesticide and drug development through gene transcription regulation by i-motif structure.
DNA 二级结构 i -motif 参与基因转录，被认为是癌症基因治疗的新靶点。i-motif 结合化合物可以稳定或破坏结构，从而导致靶基因转录的变化。在这项研究中，使用家蚕转录因子 BmPOUM2 的 i-motif 结构对 3642 种化合物进行了大规模的结合化合物筛选。表面等离子体共振成像 (SPRi) 高通量结合筛选发现 60 种化合物的结合亲和力 K 为 10-10 M。SPRi 和圆二色性 (CD) 双重筛选表明，BmPOUM2 i-motif 结构与化合物 IF1、IF3、IF4、IF6 和 IF7 的结合亲和力 K 为 10 M，与化合物 IF2 和四（4-N-甲基吡啶基）卟啉（TMPyP4）的结合亲和力 K 为 10 M。有趣的是，IF2、IF3、IF4、IF6 和 IF7 促进了 i-motif 结合蛋白 BmILF 与 i-motif 结构的结合，而 TMPyP4 则抑制了这种结合。这项研究提供了一份可能应用于 i-motif 结构功能分析以及通过 i-motif 结构调节基因转录开发农药和药物的化合物列表。
