Ma Zhongyao, Zou Bin, Zhao Jiannan, Zhang Rui, Zhu Qiaoqiao, Wang Xiaofeng, Xu Linan, Gao Xiang, Hu Xinyue, Feng Wei, Luo Wen, Wang Min, He Yunyun, Yu Zhifeng, Cui Weiren, Zhang Qi, Kuai Letian, Su Wenji
WuXi AppTec, 288 Fute Zhong Road, Waigaoqiao Free Trade Zone, Shanghai 200131, China.
WuXi AppTec, 55 Cambridge Parkway, 8th Floor, Cambridge, MA 02142, United States.
SLAS Discov. 2025 Mar;31:100204. doi: 10.1016/j.slasd.2024.100204. Epub 2024 Dec 21.
To date, RNA-targeted chemical matter is under explored due to a lack of robust screening assays. In this study, we present a novel RNA-targeted small molecule screening approach using a specialized DNA-encoded library (DEL). Our findings reveal that the specialized DEL library, called "DEL Zipper", can significantly reduce single-stranded DNA-RNA region interaction signals during various kinds of RNA selection. By performing the selection against both G-quadruplex, we have identified novel hits that interact with RNA targets and the results are validated through binding. This study demonstrates that the "DEL Zipper" method is a robust screening assay that has potential for discovering small molecule ligands for diverse RNA targets.
迄今为止，由于缺乏可靠的筛选检测方法，针对RNA的化学物质尚未得到充分探索。在本研究中，我们提出了一种使用特殊DNA编码文库（DEL）的新型RNA靶向小分子筛选方法。我们的研究结果表明，名为“DEL Zipper”的特殊DEL文库在各种RNA筛选过程中可显著降低单链DNA-RNA区域相互作用信号。通过针对G-四链体进行筛选，我们鉴定出了与RNA靶标相互作用的新型命中物，并通过结合进行了验证。本研究表明，“DEL Zipper”方法是一种可靠的筛选检测方法，具有发现针对多种RNA靶标的小分子配体的潜力。
