Development of a DNA-encoded library screening method “DEL Zipper” to empower the study of RNA-targeted chemical matter

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.

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Publication Details

Journal
SLAS DISCOVERY
Published
2024-12-21
DOI
https://doi.org/10.1016/j.slasd.2024.100204
Citations
10
Primary Topic
RNA and protein synthesis mechanisms
Type
article
Field-Weighted Citation Impact
2.34
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Development of a DNA-encoded library screening method “DEL Zipper” to empower the study of RNA-targeted chemical matter

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Development of a DNA-encoded library screening method “DEL Zipper” to empower the study of RNA-targeted chemical matter

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article en
10 citations

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.

SLAS DISCOVERYVol. 31
WuXi AppTec (China) (CN), WuXi AppTec (United States) (US)
Openalex Percentile: Top 11%
RNA and protein synthesis mechanisms
2.34
DOIOpen Access PDFOpenAlex
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