ArticleNucleic acids research2019
An ultra-high affinity ligand of HIV-1 TAR reveals the RNA structure recognized by P-TEFb.
Article in Nucleic acids research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 33 papers.
What it found
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Who cites it
33 citing papers in PubMed, 56 citations in OpenAlex.
- Detecting and quantifying overparametrization in RNA language models with REDIAL.bioRxiv : the preprint server for biology · 2026Article
- Structure-based virtual screening and molecular dynamics elucidate novel inhibitors of HIV-1 TAR RNA from enamine library.Scientific reports · 2026Article
- NMR-Based Fragment Screening for RNA-Targeted Drug Discovery.Molecules (Basel, Switzerland) · 2026Review
- The kinase inhibitor palbociclib binds to HIV TAR RNA with very low nanomolar affinity and exquisite specificity.Nucleic acids research · 2026Article
- Three-dimensional structure of the palbociclib-HIV TAR complex.Nucleic acids research · 2026Article
- Structures of complete HIV-1 TAR RNA portray a dynamic platform poised for protein binding and structural remodeling.Nature communications · 2025Article
- AI-integrated network for RNA complex structure and dynamic prediction.Biophysics reviews · 2024Review
- Tackling Undruggable Targets with Designer Peptidomimetics and Synthetic Biologics.Chemical reviews · 2024Review
- Structure-based virtual screening of unbiased and RNA-focused libraries to identify new ligands for the HCV IRES model system.RSC medicinal chemistry · 2024Article
- Structural and computational studies of HIV-1 RNA.RNA biology · 2024Review
- HIV-1 Transcription Inhibition Using Small RNA-Binding Molecules.Pharmaceuticals (Basel, Switzerland) · 2023Article
- RNet: a network strategy to predict RNA binding preferences.Briefings in bioinformatics · 2023Article
- Drug-Like Small Molecules That Inhibit Expression of the Oncogenic MicroRNA-21.ACS chemical biology · 2023Article
- PI3K/ c-Myc/AFF4 axis promotes pancreatic tumorigenesis through fueling nucleotide metabolism.International journal of biological sciences · 2023Article
- SILCS-RNA: Toward a Structure-Based Drug Design Approach for Targeting RNAs with Small Molecules.Journal of chemical theory and computation · 2022Article
- Deep structural insights into RNA-binding disordered protein regions.Wiley interdisciplinary reviews. RNA · 2022Review
- A Slow Dynamic RNA Switch Regulates Processing of microRNA-21.Journal of molecular biology · 2022Article
- Role of Mutations in Differential Recognition of Viral RNA Molecules by Peptides.Journal of chemical information and modeling · 2022Article
- RNA-Binding Macrocyclic Peptides.Frontiers in molecular biosciences · 2022Review
- Cure and Long-Term Remission Strategies.Methods in molecular biology (Clifton, N.J.) · 2022Review
Corrections and comments
- Erratum issued
Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
The HIV-1 trans-activator protein Tat binds the trans-activation response element (TAR) to facilitate recruitment of the super elongation complex (SEC) to enhance transcription of the integrated pro-viral genome. The Tat-TAR interaction is critical for viral replication and the emergence of the virus from the latent state, therefore, inhibiting this interaction has long been pursued to discover new anti-viral or latency reversal agents. However, discovering active compounds that directly target RNA with high affinity and selectivity remains a significant challenge; limiting pre-clinical development. Here, we report the rational design of a macrocyclic peptide mimic of the arginine rich motif of Tat, which binds to TAR with low pM affinity and 100-fold selectivity against closely homologous RNAs. Despite these unprecedented binding properties, the new ligand (JB181) only moderately inhibits Tat-dependent reactivation in cells and recruitment of positive transcription elongation factor (P-TEFb) to TAR. The NMR structure of the JB181-TAR complex revealed that the ligand induces a structure in the TAR loop that closely mimics the P-TEFb/Tat1:57/AFF4/TAR complex. These results strongly suggest that high-affinity ligands which bind the UCU bulge are not likely to inhibit recruitment of the SEC and suggest that targeting of the TAR loop will be an essential feature of effective Tat inhibitors.
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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.