ArticleNucleic acids research2005
Intercalator conjugates of pyrimidine locked nucleic acid-modified triplex-forming oligonucleotides: improving DNA binding properties and reaching cellular activities.
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 10 papers.
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Who cites it
10 citing papers in PubMed, 33 citations in OpenAlex.
- Versatile and efficient chromatin pull-down methodology based on DNA triple helix formation.Scientific reports · 2018Article
- LNA modification of single-stranded DNA oligonucleotides allows subtle gene modification in mismatch-repair-proficient cells.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- An innovative platform for quick and flexible joining of assorted DNA fragments.Scientific reports · 2016Article
- Review
- High-affinity triplex targeting of double stranded DNA using chemically modified peptide nucleic acid oligomers.Nucleic acids research · 2009Article
- Polypurine hairpins directed against the template strand of DNA knock down the expression of mammalian genes.The Journal of biological chemistry · 2009Article
- Triplex-forming oligonucleotide-orthophenanthroline conjugates for efficient targeted genome modification.Proceedings of the National Academy of Sciences of the United States of America · 2008Article
- Sequence-specific triple helix formation with genomic DNA.Biochemistry · 2007Article
- Bioconjugation of oligonucleotides for treating liver fibrosis.Oligonucleotides · 2007Review
- Targeting chromosomal sites with locked nucleic acid-modified triplex-forming oligonucleotides: study of efficiency dependence on DNA nuclear environment.Nucleic acids research · 2006Article
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Triplex-forming oligonucleotides (TFOs) are powerful tools to interfere sequence-specifically with DNA-associated biological functions. (A/T,G)-containing TFOs are more commonly used in cells than (T,C)-containing TFOs, especially C-rich sequences; indeed the low intracellular stability of the non-covalent pyrimidine triplexes make the latter less active. In this work we studied the possibility to enhance DNA binding of (T,C)-containing TFOs, aiming to reach cellular activities; to this end, we used locked nucleic acid-modified TFOs (TFO/LNAs) in association with 5'-conjugation of an intercalating agent, an acridine derivative. In vitro a stable triplex was formed with the TFO-acridine conjugate: by SPR measurements at 37 degrees C and neutral pH, the dissociation equilibrium constant was found in the nanomolar range and the triplex half-life approximately 10 h (50-fold longer compared with the unconjugated TFO/LNA). Moreover to further understand DNA binding of (T,C)-containing TFO/LNAs, hybridization studies were performed at different pH values: triplex stabilization associated with pH decrease was mainly due to a slower dissociation process. Finally, biological activity of pyrimidine TFO/LNAs was evaluated in a cellular context: it occurred at concentrations approximately 0.1 microM for acridine-conjugated TFO/LNA (or approximately 2 microM for the unconjugated TFO/LNA) whereas the corresponding phosphodiester TFO was inactive, and it was demonstrated to be triplex-mediated.
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