ArticleNucleic acids research2009
Two-dimensional combinatorial screening and the RNA Privileged Space Predictor program efficiently identify aminoglycoside-RNA hairpin loop interactions.
Article in Nucleic acids research, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed.
- Secondary structures that regulate mRNA translation provide insights for ASO-mediated modulation of cardiac hypertrophy.Nature communications · 2023Article
- Native Top-Down Mass Spectrometry Uncovers Two Distinct Binding Motifs of a Functional Neomycin-Sensing Riboswitch Aptamer.Journal of the American Chemical Society · 2023Article
- Secondary structures that regulate mRNA translation provide insights for ASO-mediated modulation of cardiac hypertrophy.bioRxiv : the preprint server for biology · 2023Article
- Contemporary Progress and Opportunities in RNA-Targeted Drug Discovery.ACS medicinal chemistry letters · 2023Review
- Article
- New trends in aminoglycosides use.MedChemComm · 2014Article
- Identification of biologically active, HIV TAR RNA-binding small molecules using small molecule microarrays.Journal of the American Chemical Society · 2014Article
- Defining RNA motif-aminoglycoside interactions via two-dimensional combinatorial screening and structure-activity relationships through sequencing.Bioorganic & medicinal chemistry · 2013Article
- Probing a 2-aminobenzimidazole library for binding to RNA internal loops via two-dimensional combinatorial screening.ACS chemical biology · 2012Article
- A small molecule that targets r(CGG)(exp) and improves defects in fragile X-associated tremor ataxia syndrome.ACS chemical biology · 2012Article
- Identifying the preferred RNA motifs and chemotypes that interact by probing millions of combinations.Nature communications · 2012Article
- Defining the RNA internal loops preferred by benzimidazole derivatives via 2D combinatorial screening and computational analysis.Journal of the American Chemical Society · 2011Article
- Molecular recognition of 6'-N-5-hexynoate kanamycin A and RNA 1x1 internal loops containing CA mismatches.Biochemistry · 2011Article
- Structure-activity relationships through sequencing (StARTS) defines optimal and suboptimal RNA motif targets for small molecules.Angewandte Chemie (International ed. in English) · 2010Article
- Two-dimensional combinatorial screening of a bacterial rRNA A-site-like motif library: defining privileged asymmetric internal loops that bind aminoglycosides.Biochemistry · 2010Article
Corrections and comments
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Authors and funding
3 authors.
Funding
Abstract
Herein, we report the identification of RNA hairpin loops that bind derivatives of kanamycin A, tobramycin, neamine, and neomycin B via two-dimensional combinatorial screening, a method that screens chemical and RNA spaces simultaneously. An arrayed aminoglycoside library was probed for binding to a 6-nucleotide RNA hairpin loop library (4096 members). Members of the loop library that bound each aminoglycoside were excised from the array, amplified and sequenced. Sequences were analyzed with our newly developed RNA Privileged Space Predictor (RNA-PSP) program, which analyzes selected sequences to identify statistically significant trends. RNA-PSP identified the following unique trends: 5'UNNNC3' loops for the kanamycin A derivative (where N is any nucleotide); 5'UNNC3' loops for the tobramycin derivative; 5'UNC3' loops for the neamine derivative; and 5'UNNG3' loops for the neomycin B derivative. The affinities and selectivities of a subset of the ligand-hairpin loop interactions were determined. The selected interactions have K(d) values ranging from 10 nM to 605 nM. Selectivities ranged from 0.4 to >200-fold. Interestingly, the results from RNA-PSP are able to qualitatively predict specificity based on overlap between the RNA sequences selected for the ligands. These studies expand the information available on small molecule-RNA motif interactions, which could be useful to design ligands targeting RNA.
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