ArticleProceedings of the National Academy of Sciences of the United States of America2009
A simple ligand that selectively targets CUG trinucleotide repeats and inhibits MBNL protein binding.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 114 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
114 citing papers in PubMed, 221 citations in OpenAlex.
- DLRNA-BERTa: a transformer approach for predicting molecule-RNA binding affinities.Briefings in bioinformatics · 2026Article
- RNA-binding landscape of amiloride: large-scale profiling and structural basis of U-U mismatch recognition.RSC chemical biology · 2026Article
- Targeting Expanded CUG and CTG Repeats as a Therapeutic Approach for Myotonic Dystrophy Type 1 (DM1).ChemMedChem · 2026Review
- Synthesis of Janus Bases for Targeting C‑G and U-U Pairs of CUG-RNA Repeats Associated with Myotonic Dystrophy Type 1.ACS omega · 2025Article
- Discovery of RNA-Reactive Small Molecules Guides the Design of Electrophilic Modules for RNA-Specific Covalent Binders.Journal of the American Chemical Society · 2025Article
- Article
- Electrostatic Anchoring in RNA-Ligand Design─Dissecting the Effects of Positive Charges on Affinity, Selectivity, Binding Kinetics, and Thermodynamics.Journal of medicinal chemistry · 2025Article
- Alternative Approach to Sequence-Specific Recognition of DNA: Cooperative Stacking of Dication Dimers─Sensitivity to Compound Curvature, Aromatic Structure, and DNA Sequence.ACS chemical biology · 2025Article
- Functions of the Muscleblind-like protein family and their role in disease.Cell communication and signaling : CCS · 2025Review
- NMR structures of small molecules bound to a model of a CUG RNA repeat expansion.Bioorganic & medicinal chemistry letters · 2024Review
- NMR structures of small molecules bound to a model of an RNA CUG repeat expansion.bioRxiv : the preprint server for biology · 2024Article
- An Encodable Scaffold for Sequence-Specific Recognition of Duplex RNA.Angewandte Chemie (International ed. in English) · 2023Article
- Intracellular RNA and DNA tracking by uridine-rich internal loop tagging with fluorogenic bPNA.Nature communications · 2023Article
- NMR determination of the 2:1 binding complex of naphthyridine carbamate dimer (NCD) and CGG/CGG triad in double-stranded DNA.Nucleic acids research · 2022Article
- Synthesis of Bifacial Peptide Nucleic Acids with Diketopiperazine Backbones.Synlett : accounts and rapid communications in synthetic organic chemistry · 2022Article
- Impact of bPNA Backbone Structural Constraints and Composition on Triplex Hybridization with DNA.Chembiochem : a European journal of chemical biology · 2022Article
- Fluorescence-Based Binding Characterization of Small Molecule Ligands Targeting CUG RNA Repeats.International journal of molecular sciences · 2022Article
- A structure-specific small molecule inhibits a miRNA-200 family member precursor and reverses a type 2 diabetes phenotype.Cell chemical biology · 2022Article
- Fluorobenzene Nucleobase Analogues for Triplex-Forming Peptide Nucleic Acids.Chembiochem : a European journal of chemical biology · 2022Article
- Enhanced Triplex Hybridization of DNA and RNA via Syndiotactic Side Chain Presentation in Minimal bPNAs.Biochemistry · 2022Article
54 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
This work describes the rational design, synthesis, and study of a ligand that selectively complexes CUG repeats in RNA (and CTG repeats in DNA) with high nanomolar affinity. This sequence is considered a causative agent of myotonic dystrophy type 1 (DM1) because of its ability to sequester muscleblind-like (MBNL) proteins. Ligand 1 was synthesized in two steps from commercially available compounds, and its binding to CTG and CUG repeats in oligonucleotides studied. Isothermal titration calorimetry studies of 1 with various sequences showed a preference toward the T-T mismatch (K(d) of 390 +/- 80 nM) with a 13-, 169-, and 85-fold reduction in affinity toward single C-C, A-A, and G-G mismatches, respectively. Binding and Job analysis of 1 to multiple CTG step sequences revealed high affinity binding to every other T-T mismatch with negative cooperativity for proximal T-T mismatches. The affinity of 1 for a (CUG)(4) step provided a K(d) of 430 nM with a binding stoichiometry of 1:1. The preference for the U-U in RNA was maintained with a 6-, >143-, and >143-fold reduction in affinity toward single C-C, A-A, and G-G mismatches, respectively. Ligand 1 destabilized the complexes formed between MBNL1N and (CUG)(4) and (CUG)(12) with IC(50) values of 52 +/- 20 microM and 46 +/- 7 microM, respectively, and K(i) values of 6 +/- 2 microM and 7 +/- 1 microM, respectively. These values were only minimally altered by the addition of competitor tRNA. Ligand 1 does not destabilize the unrelated RNA-protein complexes the U1A-SL2 RNA complex and the Sex lethal-tra RNA complex. Thus, ligand 1 selectively destabilizes the MBNL1N-poly(CUG) complex.
Indexed as
Identifiers
What OpenQuestion holds
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.