ArticleProceedings of the National Academy of Sciences of the United States of America2014
Tautomerism provides a molecular explanation for the mutagenic properties of the anti-HIV nucleoside 5-aza-5,6-dihydro-2'-deoxycytidine.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
20 citing papers in PubMed, 48 citations in OpenAlex.
- Conformation-dependent lesion bypass of bulky arylamine-dG adducts generated from 2-nitrofluorene in epigenetic sequence contexts.Nucleic acids research · 2023Article
- Voltage-driven control of single-molecule keto-enol equilibrium in a two-terminal junction system.Nature communications · 2023Article
- Hyperpolarizing DNA Nucleobases via NMR Signal Amplification by Reversible Exchange.Molecules (Basel, Switzerland) · 2023Article
- Lethal Mutagenesis of RNA Viruses and Approved Drugs with Antiviral Mutagenic Activity.Viruses · 2022Review
- The BlueScreen HC assay to predict the genotoxic potential of fragrance materials.Mutagenesis · 2022Article
- Multiscale Modeling of Wobble to Watson-Crick-Like Guanine-Uracil Tautomerization Pathways in RNA.International journal of molecular sciences · 2021Article
- How Hydrogen Bonding Amplifies Isomeric Differences in Pyridones toward Strong Changes in Acidity and Tautomerism.The journal of physical chemistry. B · 2021Article
- Unnatural bases for recognition of noncoding nucleic acid interfaces.Biopolymers · 2021Review
- Structural Insights Into Tautomeric Dynamics in Nucleic Acids and in Antiviral Nucleoside Analogs.Frontiers in molecular biosciences · 2021Review
- Probing conformational transitions towards mutagenic Watson-Crick-like G·T mismatches using off-resonance sugar carbon RJournal of biomolecular NMR · 2020Article
- Environmental Effects on Guanine-Thymine Mispair Tautomerization Explored with Quantum Mechanical/Molecular Mechanical Free Energy Simulations.Journal of the American Chemical Society · 2020Article
- A dielectric and spectrophotometric study of the tautomerization of 2-hydroxypyridine and 2-mercaptopyridine in water.RSC advances · 2020Article
- Biological Evaluation of DNA Biomarkers in a Chemically Defined and Site-Specific Manner.Toxics · 2019Review
- New strategies against drug resistance to herpes simplex virus.International journal of oral science · 2016Review
- Structural Characterization of Single-Stranded DNA Monolayers Using Two-Dimensional Sum Frequency Generation Spectroscopy.The journal of physical chemistry. B · 2015Article
- Intrinsic mutagenic properties of 5-chlorocytosine: A mechanistic connection between chronic inflammation and cancer.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
- Article
- Two-dimensional IR spectroscopy of the anti-HIV agent KP1212 reveals protonated and neutral tautomers that influence pH-dependent mutagenicity.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
- Evaluation of anti-HIV-1 mutagenic nucleoside analogues.The Journal of biological chemistry · 2015Article
- Role of tautomerism in RNA biochemistry.RNA (New York, N.Y.) · 2015Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Viral lethal mutagenesis is a strategy whereby the innate immune system or mutagenic pool nucleotides increase the error rate of viral replication above the error catastrophe limit. Lethal mutagenesis has been proposed as a mechanism for several antiviral compounds, including the drug candidate 5-aza-5,6-dihydro-2'-deoxycytidine (KP1212), which causes A-to-G and G-to-A mutations in the HIV genome, both in tissue culture and in HIV positive patients undergoing KP1212 monotherapy. This work explored the molecular mechanism(s) underlying the mutagenicity of KP1212, and specifically whether tautomerism, a previously proposed hypothesis, could explain the biological consequences of this nucleoside analog. Establishing tautomerism of nucleic acid bases under physiological conditions has been challenging because of the lack of sensitive methods. This study investigated tautomerism using an array of spectroscopic, theoretical, and chemical biology approaches. Variable temperature NMR and 2D infrared spectroscopic methods demonstrated that KP1212 existed as a broad ensemble of interconverting tautomers, among which enolic forms dominated. The mutagenic properties of KP1212 were determined empirically by in vitro and in vivo replication of a single-stranded vector containing a single KP1212. It was found that KP1212 paired with both A (10%) and G (90%), which is in accord with clinical observations. Moreover, this mutation frequency is sufficient for pushing a viral population over its error catastrophe limit, as observed before in cell culture studies. Finally, a model is proposed that correlates the mutagenicity of KP1212 with its tautomeric distribution in solution.
Indexed as
Identifiers
What OpenQuestion holds
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.