Development of a DNA-encoded library screening method “DEL Zipper” to empower the study of RNA-targeted chemical matter
Zhongyao Ma, Bin Zou, Jiannan Zhao, Rui Zhang, Qiaoqiao Zhu, Xiaofeng Wang, Linan Xu, Xiang Gao, Xinyue Hu, Wei Feng, Wen Luo, Min Wang, Yunyun He, Zhifeng Yu, Weiren Cui, Qi Zhang, Letian Kuai, Wenji Su
Abstract
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.