ArticleAntiviral research2011
HPV episome levels are potently decreased by pyrrole-imidazole polyamides.
Article in Antiviral research, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 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
31 citing papers in PubMed, 61 citations in OpenAlex.
- Binding to the DNA Minor Groove by Heterocyclic Dications: from AT Specific to GC Recognition Compounds.Current protocols · 2023Review
- The Reservoir of Persistent Human Papillomavirus Infection; Strategies for Elimination Using Anti-Viral Therapies.Viruses · 2022Review
- Subversion of Host Innate Immunity by Human Papillomavirus Oncoproteins.Pathogens (Basel, Switzerland) · 2020Review
- Recent developments in compounds acting in the DNA minor groove.MedChemComm · 2019Review
- A Polyamide Inhibits Replication of Vesicular Stomatitis Virus by Targeting RNA in the Nucleocapsid.Journal of virology · 2018Article
- Structural basis of DNA duplex distortion induced by thiazole-containing hairpin polyamides.Nucleic acids research · 2018Article
- β-Alanine and N-terminal cationic substituents affect polyamide-DNA binding.Organic & biomolecular chemistry · 2017Article
- Identification of several high-risk HPV inhibitors and drug targets with a novel high-throughput screening assay.PLoS pathogens · 2017Article
- Systematic synthetic and biophysical development of mixed sequence DNA binding agents.Organic & biomolecular chemistry · 2017Article
- Synthetic genome readers target clustered binding sites across diverse chromatin states.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- Article
- Interactions of two large antiviral polyamides with the long control region of HPV16.Biochimie · 2016Article
- Genome-wide Mapping of Drug-DNA Interactions in Cells with COSMIC (Crosslinking of Small Molecules to Isolate Chromatin).Journal of visualized experiments : JoVE · 2016Article
- Fe(II)/Et3N-Relay-catalyzed domino reaction of isoxazoles with imidazolium salts in the synthesis of methyl 4-imidazolylpyrrole-2-carboxylates, its ylide and betaine derivatives.Beilstein journal of organic chemistry · 2015Article
- Recent Insights into the Control of Human Papillomavirus (HPV) Genome Stability, Loss, and Degradation.Journal of clinical medicine · 2015Article
- Controlling gene networks and cell fate with precision-targeted DNA-binding proteins and small-molecule-based genome readers.The Biochemical journal · 2014Review
- Mapping polyamide-DNA interactions in human cells reveals a new design strategy for effective targeting of genomic sites.Angewandte Chemie (International ed. in English) · 2014Article
- Article
- DNA Binding Polyamides and the Importance of DNA Recognition in their use as Gene-Specific and Antiviral Agents.Medicinal chemistry · 2014Article
- Design and synthesis of heterocyclic cations for specific DNA recognition: from AT-rich to mixed-base-pair DNA sequences.The Journal of organic chemistry · 2014Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Human papillomavirus (HPV) causes cervical cancer and other hyperproliferative diseases. There currently are no approved antiviral drugs for HPV that directly decrease viral DNA load and that have low toxicity. We report the potent anti-HPV activity of two N-methylpyrrole-imidazole polyamides of the hairpin type, polyamide 1 (PA1) and polyamide 25 (PA25). Both polyamides have potent anti-HPV activity against three different genotypes when tested on cells maintaining HPV episomes. The compounds were tested against HPV16 (in W12 cells), HPV18 (in Ker4-18 cells), and HPV31 (in HPV31 maintaining cells). From a library of polyamides designed to recognize AT-rich DNA sequences such as those in or near E1 or E2 binding sites of the HPV16 origin of replication (ori), four polyamides were identified that possessed apparent IC(50)s≤150nM with no evidence of cytotoxicity. We report two highly-active compounds here. Treatment of epithelia engineered in organotypic cultures with these compounds also causes a dose-dependent loss of HPV episomal DNA that correlates with accumulation of compounds in the nucleus. Bromodeoxyuridine (BrdU) incorporation demonstrates that DNA synthesis in organotypic cultures is suppressed upon compound treatment, correlating with a loss of HPV16 and HPV18 episomes. PA1 and PA25 are currently in preclinical development as antiviral compounds for treatment of HPV-related disease, including cervical dysplasia. PA1, PA25, and related polyamides offer promise as antiviral agents and as tools to regulate HPV episomal levels in cells for the study of HPV biology. We also report that anti-HPV16 activity for Distamycin A, a natural product related to our polyamides, is accompanied by significant cellular toxicity.
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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.