ArticleProceedings of the National Academy of Sciences of the United States of America2022
Discovery of small molecules that target a tertiary-structured RNA.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 40 citations in OpenAlex.
- Computational Analysis of Sequence Editability in the Theophylline RNA Aptamer as a Functional RNA Module.International journal of molecular sciences · 2026Article
- Reconsidering Molecular Docking Practices in Aptamer Research.Chembiochem : a European journal of chemical biology · 2026Article
- Comparative Evaluation of Explicit Solvent Models for RNA-Ligand Docking.Journal of chemical information and modeling · 2026Article
- Single Molecule Force Measurements Reveal Energy Stabilization of Theophylline Aptamer RNA Switch Required for Gene Control.ACS physical chemistry Au · 2026Article
- Engineering ligands for theophylline riboswitches expands its regulatory dynamic range in prokaryotic and eukaryotic systems.Nature communications · 2026Article
- NMR-Based Fragment Screening for RNA-Targeted Drug Discovery.Molecules (Basel, Switzerland) · 2026Review
- Ribocentre-aptamer: an integrative, structure-focused database for RNA aptamers.Nucleic acids research · 2026Article
- Predicting small molecule-RNA interactions without RNA tertiary structures.Nature biotechnology · 2026Article
- Programmable fluorescent aptamer-based RNA switches for rapid identification of point mutations.Nature chemistry · 2025Article
- Eight Triplex-Binding Molecules from Four Chemical Classes Broadly Recognize the MALAT1 Triple Helix.Molecules (Basel, Switzerland) · 2025Article
- High-throughput competitive binding assay for targeting RNA tertiary structures with small molecules: application to pseudoknots and G-quadruplexes.Nucleic acids research · 2025Article
- Direct Modeling of DNA and RNA Aptamers with AlphaFold 3: A Promising Tool for Predicting Aptamer Structures and Aptamer-Target Interactions.ACS synthetic biology · 2025Article
- Rebuttal letter of the "comment on "contrastive pre-training and 3D convolution neural network for RNA and small molecule binding affinity prediction" by Sun and Gao".Bioinformatics (Oxford, England) · 2025Article
- Comment on "Contrastive pre-training and 3D convolution neural network for RNA and small molecule binding affinity prediction" by Sun and Gao.Bioinformatics (Oxford, England) · 2025Article
- Molecular insights into de novo small-molecule recognition by an intron RNA structure.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- DRLiPS: a novel method for prediction of druggable RNA-small molecule binding pockets using machine learning.Nucleic acids research · 2025Article
- Novel Quinazoline Derivatives Inhibit Splicing of Fungal Group II Introns.ACS chemical biology · 2025Article
- Resilience Against Resistance: Exploring Cutting-edge Therapies for Methicillin-resistantCurrent medicinal chemistry · 2025Review
- A virtual system-coupled molecular dynamics simulation free from experimental knowledge on binding sites: Application to RNA-ligand binding free-energy landscape.Biophysics and physicobiology · 2025Article
- Making target sites in large structured RNAs accessible to RNA-cleaving DNAzymes through hybridization with synthetic DNA oligonucleotides.Nucleic acids research · 2024Article
Corrections and comments
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Authors and funding
17 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
There is growing interest in therapeutic intervention that targets disease-relevant RNAs using small molecules. While there have been some successes in RNA-targeted small-molecule discovery, a deeper understanding of structure-activity relationships in pursuing these targets has remained elusive. One of the best-studied tertiary-structured RNAs is the theophylline aptamer, which binds theophylline with high affinity and selectivity. Although not a drug target, this aptamer has had many applications, especially pertaining to genetic control circuits. Heretofore, no compound has been shown to bind the theophylline aptamer with greater affinity than theophylline itself. However, by carrying out a high-throughput screen of low-molecular-weight compounds, several unique hits were identified that are chemically distinct from theophylline and bind with up to 340-fold greater affinity. Multiple atomic-resolution X-ray crystal structures were determined to investigate the binding mode of theophylline and four of the best hits. These structures reveal both the rigidity of the theophylline aptamer binding pocket and the opportunity for other ligands to bind more tightly in this pocket by forming additional hydrogen-bonding interactions. These results give encouragement that the same approaches to drug discovery that have been applied so successfully to proteins can also be applied to RNAs.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.