ArticleACS chemical biology2013
Features of modularly assembled compounds that impart bioactivity against an RNA target.
Article in ACS chemical biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
What it found
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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.
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.
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Who cites it
36 citing papers in PubMed, 41 citations in OpenAlex.
- Targeting Expanded CUG and CTG Repeats as a Therapeutic Approach for Myotonic Dystrophy Type 1 (DM1).ChemMedChem · 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
- Streamlined Fragment-Based Discovery Platform for Targeting Structured RNAs.ACS chemical biology · 2025Article
- 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
- Small molecules modulating RNA splicing: a review of targets and future perspectives.RSC medicinal chemistry · 2024Review
- Massively Parallel Optimization of the Linker Domain in Small Molecule Dimers Targeting a Toxic r(CUG) Repeat Expansion.ACS medicinal chemistry letters · 2021Article
- A general fragment-based approach to identify and optimize bioactive ligands targeting RNA.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Small molecule-RNA targeting: starting with the fundamentals.Chemical communications (Cambridge, England) · 2020Article
- Macrocyclization of a Ligand Targeting a Toxic RNA Dramatically Improves Potency.Chembiochem : a European journal of chemical biology · 2020Article
- Small molecule recognition of disease-relevant RNA structures.Chemical Society reviews · 2020Review
- How We Think about Targeting RNA with Small Molecules.Journal of medicinal chemistry · 2020Article
- Gini Coefficients as a Single Value Metric to Define Chemical Probe Selectivity.ACS 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
- Mitigating RNA Toxicity in Myotonic Dystrophy using Small Molecules.International journal of molecular sciences · 2019Review
- Review
- Identifying and validating small molecules interacting with RNA (SMIRNAs).Methods in enzymology · 2019Article
- Drugging the RNA World.Cold Spring Harbor perspectives in biology · 2018Review
- Insights into the development of chemical probes for RNA.Nucleic acids research · 2018Article
- Selective Small Molecule Recognition of RNA Base Pairs.ACS combinatorial science · 2018Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Transcriptomes provide a myriad of potential RNAs that could be the targets of therapeutics or chemical genetic probes of function. Cell-permeable small molecules, however, generally do not exploit these targets, owing to the difficulty in the design of high affinity, specific small molecules targeting RNA. As part of a general program to study RNA function using small molecules, we designed bioactive, modularly assembled small molecules that target the noncoding expanded RNA repeat that causes myotonic dystrophy type 1 (DM1), r(CUG)(exp). Herein, we present a rigorous study to elucidate features in modularly assembled compounds that afford bioactivity. Different modular assembly scaffolds were investigated, including polyamines, α-peptides, β-peptides, and peptide tertiary amides (PTAs). On the basis of activity as assessed by improvement of DM1-associated defects, stability against proteases, cellular permeability, and toxicity, we discovered that constrained backbones, namely, PTAs, are optimal. Notably, we determined that r(CUG)(exp) is the target of the optimal PTA in cellular models and that the optimal PTA improves DM1-associated defects in a mouse model. Biophysical analyses were employed to investigate potential sources of bioactivity. These investigations show that modularly assembled compounds have increased residence times on their targets and faster on rates than the RNA-binding modules from which they were derived. Moreover, they have faster on rates than the protein that binds r(CUG)(exp), the inactivation of which gives rise to DM1-associated defects. These studies provide information about features of small molecules that are programmable for targeting RNA, allowing for the facile optimization of therapeutics or chemical probes against other cellular RNA targets.
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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.