ArticleCell chemical biology2020
Parallel Discovery Strategies Provide a Basis for Riboswitch Ligand Design.
Article in Cell chemical biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 33 citations in OpenAlex.
- Carboxamide: A Privileged Pharmacophore for the Development of Anti-infectious and Anti-cancer Drugs.Current topics in medicinal chemistry · 2026Review
- Functional Relevance of CASP16 Nucleic Acid Predictions as Evaluated by Structure Providers.Proteins · 2026Article
- Machine Learning-Augmented Molecular Dynamics Simulations (MD) Reveal Insights Into the Disconnect Between Affinity and Activation of ZTP Riboswitch Ligands.Angewandte Chemie (International ed. in English) · 2025Article
- Mechanistic studies of small molecule ligands selective to RNA single G bulges.Nucleic acids research · 2025Article
- Functional relevance of CASP16 nucleic acid predictions as evaluated by structure providers.bioRxiv : the preprint server for biology · 2025Article
- Systematic analysis of cotranscriptional RNA folding using transcription elongation complex display.Nature communications · 2025Article
- RNA folding kinetics control riboswitch sensitivity in vivo.Nature communications · 2025Article
- Opportunities for Riboswitch Inhibition by Targeting Co-Transcriptional RNA Folding Events.International journal of molecular sciences · 2024Review
- Mechanistic analysis of Riboswitch Ligand interactions provides insights into pharmacological control over gene expression.Nature communications · 2024Article
- A sensitive and scalable fluorescence anisotropy single stranded RNA targeting approach for monitoring riboswitch conformational states.Nucleic acids research · 2024Article
- RNA folding kinetics control riboswitch sensitivity in vivo.bioRxiv : the preprint server for biology · 2024Article
- Contrastive pre-training and 3D convolution neural network for RNA and small molecule binding affinity prediction.Bioinformatics (Oxford, England) · 2024Article
- Mechanistic Analysis of Riboswitch Ligand Interactions Provides Insights into Pharmacological Control over Gene Expression.bioRxiv : the preprint server for biology · 2024Article
- Targeting RNA structures with small molecules.Nature reviews. Drug discovery · 2022Review
- Enhanced cobalamin biosynthesis inSynthetic and systems biotechnology · 2022Article
- RNA-Ligand Interactions Quantified by Surface Plasmon Resonance with Reference Subtraction.Biochemistry · 2022Article
- Subsite Ligand Recognition and Cooperativity in the TPP Riboswitch: Implications for Fragment-Linking in RNA Ligand Discovery.ACS chemical biology · 2022Article
- Small molecule targeting of biologically relevant RNA tertiary and quaternary structures.Cell chemical biology · 2021Review
- Synthesis of RNA-based gene regulatory devices for redirecting cellular signaling events mediated by p53.Theranostics · 2021Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
Riboswitches are mRNA domains that make gene-regulatory decisions upon binding their cognate ligands. Bacterial riboswitches that specifically recognize 5-aminoimidazole-4-carboxamide riboside 5'-monophosphate (ZMP) and 5'-triphosphate (ZTP) regulate genes involved in folate and purine metabolism. Now, we have developed synthetic ligands targeting ZTP riboswitches by replacing the sugar-phosphate moiety of ZMP with various functional groups, including simple heterocycles. Despite losing hydrogen bonds from ZMP, these analogs bind ZTP riboswitches with similar affinities as the natural ligand, and activate transcription more strongly than ZMP in vitro. The most active ligand stimulates gene expression ∼3 times more than ZMP in a live Escherichia coli reporter. Co-crystal structures of the Fusobacterium ulcerans ZTP riboswitch bound to synthetic ligands suggest stacking of their pyridine moieties on a conserved RNA nucleobase primarily determines their higher activity. Altogether, these findings guide future design of improved riboswitch activators and yield insights into how RNA-targeted ligand discovery may proceed.
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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.