ArticleThe journal of physical chemistry. B2013
Effects of hypoxanthine substitution in peptide nucleic acids targeting KRAS2 oncogenic mRNA molecules: theory and experiment.
Article in The journal of physical chemistry. B, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 32 citations in OpenAlex.
- IGF1R-targeted delivery of a bridged nucleic acid oligonucleotide-peptide conjugate for microRNA-21 inhibition in triple-negative breast cancer.NAR cancer · 2025Article
- Exploring the DNAHeliyon · 2024Article
- Parameterization of the miniPEG-Modified γPNA Backbone: Toward Induced γPNA Duplex Dissociation.Journal of chemical theory and computation · 2023Article
- Antibacterial Peptide Nucleic Acids-Facts and Perspectives.Molecules (Basel, Switzerland) · 2020Review
- Structural Insights on Tiny Peptide Nucleic Acid (PNA) Analogues of miRNA-34a: AnFrontiers in chemistry · 2020Article
- Peptide nucleic acids: Advanced tools for biomedical applications.Journal of biotechnology · 2017Review
- Peptide Nucleic Acids as miRNA Target Protectors for the Treatment of Cystic Fibrosis.Molecules (Basel, Switzerland) · 2017Article
- Focus on PNA Flexibility and RNA Binding using Molecular Dynamics and Metadynamics.Scientific reports · 2017Article
- Non-Specific Blocking of miR-17-5p Guide Strand in Triple Negative Breast Cancer Cells by Amplifying Passenger Strand Activity.PloS one · 2015Article
- Fluorescence detection of KRAS2 mRNA hybridization in lung cancer cells with PNA-peptides containing an internal thiazole orange.Bioconjugate chemistry · 2014Article
- Exploitation of a very small peptide nucleic acid as a new inhibitor of miR-509-3p involved in the regulation of cystic fibrosis disease-gene expression.BioMed research international · 2014Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
Abstract
Genetic disorders can arise from single base substitutions in a single gene. A single base substitution for wild type guanine in the twelfth codon of KRAS2 mRNA occurs frequently to initiate lung, pancreatic, and colon cancer. We have observed single base mismatch specificity in radioimaging of mutant KRAS2 mRNA in tumors in mice by in vivo hybridization with radiolabeled peptide nucleic acid (PNA) dodecamers. We hypothesized that multimutant specificity could be achieved with a PNA dodecamer incorporating hypoxanthine, which can form Watson-Crick base pairs with adenine, cytosine, thymine, and uracil. Using molecular dynamics simulations and free energy calculations, we show that hypoxanthine substitutions in PNAs are tolerated in KRAS2 RNA:PNA duplexes where wild type guanine is replaced by mutant uracil or adenine in RNA. To validate our predictions, we synthesized PNA dodecamers with hypoxanthine, and then measured the thermal stability of RNA:PNA duplexes. Circular dichroism thermal melting results showed that hypoxanthine-containing PNAs are more stable in duplexes where hypoxanthine-adenine and hypoxanthine-uracil base pairs are formed than single mismatch duplexes or duplexes containing hypoxanthine-guanine opposition.
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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.