ArticleNucleic acids research2022
Expanding the DNA-encoded library toolbox: identifying small molecules targeting RNA.
Article in Nucleic acids research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 38 citations in OpenAlex.
- Unleashing the power of DNA-encoded libraries for challenging targets in drug discovery.Pharmaceutical science advances · 2026Review
- RNA-Focused DNA-Encoded Library Construction, Screening, and Integration of Docking Identify Bioactive Ligands of Pathogenic r(GbioRxiv : the preprint server for biology · 2025Article
- Enabling Open Machine Learning of Deoxyribonucleic Acid-Encoded Library Selections to Accelerate the Discovery of Small Molecule Protein Binders.Journal of medicinal chemistry · 2025Article
- Discovery of Macrocyclic Peptide Binders, Covalent Modifiers, and Degraders of a Structured RNA by mRNA Display.Journal of the American Chemical Society · 2025Article
- Open-Source DNA-Encoded Library informatics Package for Design, Decoding, and Analysis: DELi.bioRxiv : the preprint server for biology · 2025Article
- Review
- The Druggable Transcriptome Project: From Chemical Probes to Precision Medicines.Biochemistry · 2025Review
- New strategies to enhance the efficiency and precision of drug discovery.Frontiers in pharmacology · 2025Review
- Fluorescent Ligand Equilibrium Displacement: A High-Throughput Method for Identification of FMN Riboswitch-Binding Small Molecules.International journal of molecular sciences · 2024Article
- EasyDock: customizable and scalable docking tool.Journal of cheminformatics · 2023Article
- Small-molecule discovery through DNA-encoded libraries.Nature reviews. Drug discovery · 2023Review
- A Riboswitch-Driven Era of New Antibacterials.Antibiotics (Basel, Switzerland) · 2022Review
Corrections and comments
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Authors and funding
11 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
DNA-encoded library (DEL) technology is a powerful tool for small molecule identification in drug discovery, yet the reported DEL selection strategies were applied primarily on protein targets in either purified form or in cellular context. To expand the application of this technology, we employed DEL selection on an RNA target HIV-1 TAR (trans-acting responsive region), but found that the majority of signals were resulted from false positive DNA-RNA binding. We thus developed an optimized selection strategy utilizing RNA patches and competitive elution to minimize unwanted DNA binding, followed by k-mer analysis and motif search to differentiate false positive signal. This optimized strategy resulted in a very clean background in a DEL selection against Escherichia coli FMN Riboswitch, and the enriched compounds were determined with double digit nanomolar binding affinity, as well as similar potency in functional FMN competition assay. These results demonstrated the feasibility of small molecule identification against RNA targets using DEL selection. The developed experimental and computational strategy provided a promising opportunity for RNA ligand screening and expanded the application of DEL selection to a much wider context in drug discovery.
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