ArticleNucleic acids research1997
Binding of Hoechst 33258 to the TAR RNA of HIV-1. Recognition of a pyrimidine bulge-dependent structure.
Article in Nucleic acids research, 1997. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 67 citations in OpenAlex.
- The kinase inhibitor palbociclib binds to HIV TAR RNA with very low nanomolar affinity and exquisite specificity.Nucleic acids research · 2026Article
- Targeting RNA with small molecules, from RNA structures to precision medicines: IUPHAR review: 40.British journal of pharmacology · 2024Review
- Contemporary Progress and Opportunities in RNA-Targeted Drug Discovery.ACS medicinal chemistry letters · 2023Review
- Effect of single-residue bulges on RNA double-helical structures: crystallographic database analysis and molecular dynamics simulation studies.Journal of molecular modeling · 2017Article
- Development of Small Molecules with a Noncanonical Binding Mode to HIV-1 Trans Activation Response (TAR) RNA.Journal of medicinal chemistry · 2016Article
- Multivalency in the recognition and antagonism of a HIV TAR RNA-TAT assembly using an aminoglycoside benzimidazole scaffold.Organic & biomolecular chemistry · 2016Article
- Potent inhibition of miR-27a by neomycin-bisbenzimidazole conjugates.Chemical science · 2015Article
- Multivalent Amino Sugars to Recognize Different TAR RNA Conformations.MedChemComm · 2014Article
- Novel neuroprotective GSK-3β inhibitor restricts Tat-mediated HIV-1 replication.Journal of virology · 2014Article
- Recognition of HIV-TAR RNA using neomycin-benzimidazole conjugates.Bioorganic & medicinal chemistry letters · 2013Article
- Click dimers to target HIV TAR RNA conformation.Biochemistry · 2012Article
- Recognition of HIV TAR RNA by triazole linked neomycin dimers.Bioorganic & medicinal chemistry letters · 2011Article
- Defining the RNA internal loops preferred by benzimidazole derivatives via 2D combinatorial screening and computational analysis.Journal of the American Chemical Society · 2011Article
- Inhibition of Tat-mediated HIV-1 replication and neurotoxicity by novel GSK3-beta inhibitors.Virology · 2011Article
- Interaction of anthracyclines with iron responsive element mRNAs.Nucleic acids research · 2008Article
- Liquid-crystal NMR structure of HIV TAR RNA bound to its SELEX RNA aptamer reveals the origins of the high stability of the complex.Proceedings of the National Academy of Sciences of the United States of America · 2008Article
- The up-regulation of ferritin expression using a small-molecule ligand to the native mRNA.Proceedings of the National Academy of Sciences of the United States of America · 2006Article
- Activity of Hoechst 33258 against Pneumocystis carinii f. sp. muris, Candida albicans, and Candida dubliniensis.Antimicrobial agents and chemotherapy · 2005Article
- V, 2.Ribosomal frameshifting in astroviruses.Perspectives in medical virology · 2003Article
- Inhibition of translation by RNA-small molecule interactions.RNA (New York, N.Y.) · 2002Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The transactivation response region (TAR) RNA is an essential component in transcriptional regulation of the human immunodeficiency virus type-1 (HIV-1) genome. We have examined the interaction between TAR RNA and the bisbenzimidazole derivative Hoechst 33258. Previous studies have shown that this drug, which is well known as an AT-selective DNA minor groove binder, can also interact with GC-rich sequences in DNA as well as with RNA, possibly by intercalation. Absorption spectroscopy, circular dichroism and electric linear dichroism, as well as RNase A footprinting, were employed to compare binding of Hoechst 33258 to wild-type RNA and its analogue lacking the pyrimidine bulge. The uridine bulge, which is an important contributor to the structural stability of TAR, plays an essential role in drug binding. Deletion of the bulge destabilizes both free and drug-bound forms of TAR and markedly affects the orientation of the drug chromophore complexed with the RNA. According to the linear dichroism data, the bisbenzimidazole is oriented more or less perpendicular to the RNA helix axis. The data are compatible with a model in which the bisbenzimidazole chromophore is inserted into the existing cavity created by the pyrimidine bulge. The footprinting experiments, showing that the drug binds to a unique site opposite the unpaired uridine residues, also support this model. The binding of Hoechst 33258 to the sequence 5'-GCUCU, which delimits the cavity, reflects the greater accessibility of that region compared with other sites in the RNA molecule. The identification of a binding site for small molecules in TAR offers promising perspectives for developing drugs that would block the access of TAR RNA to proteins and therefore for the design of anti-HIV agents.
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