ArticleNucleic acids research2005
Cell-penetrating peptide conjugates of peptide nucleic acids (PNA) as inhibitors of HIV-1 Tat-dependent trans-activation in cells.
Article in Nucleic acids research, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 84 papers.
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Who cites it
84 citing papers in PubMed, 232 citations in OpenAlex.
- Modulating the cleavage and polyadenylation site: from research tools to therapeutic opportunities.RNA (New York, N.Y.) · 2026Review
- Gamma-FIT-PNAs as sensitive RNA probes.RSC chemical biology · 2026Article
- Molecular properties and intramolecular interactions of peptide-conjugated phosphorodiamidate morpholino oligonucleotides.Molecular therapy. Nucleic acids · 2025Article
- Harnessing BET-Bromodomain Assisted Nuclear Import for Targeted Subcellular Localization and Enhanced Efficacy of Antisense Oligonucleotides.Journal of the American Chemical Society · 2025Article
- 7-Methylguanine With a Cyclopentane Backbone: A Bright Combination for a FIT-PNA RNA Sensor.British journal of biomedical science · 2025Article
- Targeting RNA with synthetic oligonucleotides: Clinical success invites new challenges.Cell chemical biology · 2024Review
- Peptide nucleic acid conjugates and their antimicrobial applications-a mini-review.European biophysics journal : EBJ · 2023Review
- Application of Cell Penetrating Peptides as a Promising Drug Carrier to Combat Viral Infections.Molecular biotechnology · 2023Review
- Self-transfecting GMO-PMO chimera targetingMolecular therapy. Nucleic acids · 2023Article
- A Review of Protein- and Peptide-Based Chemical Conjugates: Past, Present, and Future.Pharmaceutics · 2023Review
- Recent Development in Biomedical Applications of Oligonucleotides with Triplex-Forming Ability.Polymers · 2023Review
- Antiviral Peptide-Based Conjugates: State of the Art and Future Perspectives.Pharmaceutics · 2023Review
- Antispacer peptide nucleic acids for sequence-specific CRISPR-Cas9 modulation.Nucleic acids research · 2022Article
- Cellular uptake of 2-aminopyridine-modified peptide nucleic acids conjugated with cell-penetrating peptides.Biopolymers · 2022Article
- Head on Comparison of Self- and Nano-assemblies of Gamma Peptide Nucleic Acid Amphiphiles.Advanced functional materials · 2022Article
- Therapeutic Potential of Chemically Modified, Synthetic, Triplex Peptide Nucleic Acid-Based Oncomir Inhibitors for Cancer Therapy.Cancer research · 2021Article
- Gene-specific MicroRNA antagonism protects against HIV Tat and TGF-β-mediated suppression of CFTR mRNA and function.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2021Article
- Extracellular vesicles mediated exocytosis of antisense peptide nucleic acids.Molecular therapy. Nucleic acids · 2021Article
- Pyridazine Nucleobase in Triplex-Forming PNA Improves Recognition of Cytosine Interruptions of Polypurine Tracts in RNA.ACS chemical biology · 2021Article
- Can Vitamin B12 Assist the Internalization of Antisense LNA Oligonucleotides into Bacteria?Antibiotics (Basel, Switzerland) · 2021Article
24 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The trans-activation response (TAR) RNA stem-loop that occurs at the 5' end of HIV RNA transcripts is an important antiviral target and is the site of interaction of the HIV-1 Tat protein together with host cellular factors. Oligonucleotides and their analogues targeted to TAR are potential antiviral candidates. We have investigated a range of cell penetrating peptide (CPP) conjugates of a 16mer peptide nucleic acid (PNA) analogue targeted to the apical stem-loop of TAR and show that disulfide-linked PNA conjugates of two types of CPP (Transportan or a novel chimeric peptide R6-Penetratin) exhibit dose-dependent inhibition of Tat-dependent trans-activation in a HeLa cell assay when incubated for 24 h. Activity is reached within 6 h if the lysosomotropic reagent chloroquine is co-administered. Fluorescein-labelled stably-linked conjugates of Tat, Transportan or Transportan TP10 with PNA were inactive when delivered alone, but attained trans-activation inhibition in the presence of chloroquine. Confocal microscopy showed that such fluorescently labelled CPP-PNA conjugates were sequestered in endosomal or membrane-bound compartments of HeLa cells, which varied in appearance depending on the CPP type. Co-administration of chloroquine was seen in some cases to release fluorescence from such compartments into the nucleus, but with different patterns depending on the CPP. The results show that CPP-PNA conjugates of different types can inhibit Tat-dependent trans-activation in HeLa cells and have potential for development as antiviral agents. Endosomal or membrane release is a major factor limiting nuclear delivery and trans-activation inhibition.
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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.