ArticleACS chemical biology2012
Chemical correction of pre-mRNA splicing defects associated with sequestration of muscleblind-like 1 protein by expanded r(CAG)-containing transcripts.
Article in ACS chemical biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
53 citing papers in PubMed, 73 citations in OpenAlex.
- Predicting small molecule-RNA interactions without RNA tertiary structures.Nature biotechnology · 2026Article
- NMR structures of small molecules bound to a model of a CUG RNA repeat expansion.Bioorganic & medicinal chemistry letters · 2024Review
- NMR structures and magnetic force spectroscopy studies of small molecules binding to models of an RNA CAG repeat expansion.bioRxiv : the preprint server for biology · 2024Article
- NMR structures of small molecules bound to a model of an RNA CUG repeat expansion.bioRxiv : the preprint server for biology · 2024Article
- Targeting RNA structures with small molecules.Nature reviews. Drug discovery · 2022Review
- Fluorescence-Based Binding Characterization of Small Molecule Ligands Targeting CUG RNA Repeats.International journal of molecular sciences · 2022Article
- Small Molecule Screening Discovers Compounds that Reduce FMRpolyG Protein Aggregates and Splicing Defect Toxicity in Fragile X-Associated Tremor/Ataxia Syndrome.Molecular neurobiology · 2022Article
- Role and Perspective of Molecular Simulation-Based Investigation of RNA-Ligand Interaction: From Small Molecules and Peptides to Photoswitchable RNA Binding.Molecules (Basel, Switzerland) · 2021Review
- CAG RNAs induce DNA damage and apoptosis by silencingProceedings of the National Academy of Sciences of the United States of America · 2021Article
- Macrocyclization of a Ligand Targeting a Toxic RNA Dramatically Improves Potency.Chembiochem : a European journal of chemical biology · 2020Article
- Optimization of the Linker Domain in a Dimeric Compound that Degrades an r(CUG) Repeat Expansion in Cells.Journal of medicinal chemistry · 2020Article
- Small molecule targeting of RNA structures in neurological disorders.Annals of the New York Academy of Sciences · 2020Review
- Curcumin Regulates the r(CGG)Frontiers in neuroscience · 2020Article
- Exploring the Potential of Small Molecule-Based Therapeutic Approaches for Targeting Trinucleotide Repeat Disorders.Molecular neurobiology · 2020Review
- Discovery of a potent small molecule inhibiting Huntington's disease (HD) pathogenesis via targeting CAG repeats RNA and Poly Q protein.Scientific reports · 2019Article
- A CTG repeat-selective chemical screen identifies microtubule inhibitors as selective modulators of toxic CUG RNA levels.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Short Tandem Repeat Expansions and RNA-Mediated Pathogenesis in Myotonic Dystrophy.International journal of molecular sciences · 2019Review
- Shape similarity guided pose prediction: lessons from D3R Grand Challenge 3.Journal of computer-aided molecular design · 2019Article
- Identifying and validating small molecules interacting with RNA (SMIRNAs).Methods in enzymology · 2019Article
- Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
Recently, it was reported that expanded r(CAG) triplet repeats (r(CAG)(exp)) associated with untreatable neurological diseases cause pre-mRNA mis-splicing likely due to sequestration of muscleblind-like 1 (MBNL1) splicing factor. Bioactive small molecules that bind the 5'CAG/3'GAC motif found in r(CAG)(exp) hairpin structure were identified by using RNA binding studies and virtual screening/chemical similarity searching. Specifically, a benzylguanidine-containing small molecule was found to improve pre-mRNA alternative splicing of MBNL1-sensitive exons in cells expressing the toxic r(CAG)(exp). The compound was identified by first studying the binding of RNA 1 × 1 nucleotide internal loops to small molecules known to have affinity for nucleic acids. Those studies identified 4',6-diamidino-2-phenylindole (DAPI) as a specific binder to RNAs with the 5'CAG/3'GAC motif. DAPI was then used as a query molecule in a shape- and chemistry alignment-based virtual screen to identify compounds with improved properties, which identified 4-guanidinophenyl 4-guanidinobenzoate, a small molecule that improves pre-mRNA splicing defects associated with the r(CAG)(exp)-MBNL1 complex. This compound may facilitate the development of therapeutics to treat diseases caused by r(CAG)(exp) and could serve as a useful chemical tool to dissect the mechanisms of r(CAG)(exp) toxicity. The approach used in these studies, defining the small RNA motifs that bind small molecules with known affinity for nucleic acids and then using virtual screening to optimize them for bioactivity, may be generally applicable for designing small molecules that target other RNAs in the human genomic sequence.
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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.