Evidence map›Paper›PMID 18456705›Full record

ArticleNucleic acids research2008

Purine twisted-intercalating nucleic acids: a new class of anti-gene molecules resistant to potassium-induced aggregation.

Manikandan Paramasivam, Susanna Cogoi, Vyacheslav V Filichev, Niels Bomholt, Erik B Pedersen, Luigi E Xodo

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
1.9field-weighted citation impact, top 15% of its field
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

17 citing papers in PubMed, 46 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 1 institution in 1 country.

Manikandan ParamasivamDepartment of Biochemical Science and Technology, P.le Kolbe 4, 33100 Udine, Italy.
Susanna Cogoi
Vyacheslav V Filichev
Niels Bomholt
Erik B Pedersen
Luigi E Xodo
Massey University · NZ

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Sequence-specific targeting of genomic DNA by triplex-forming oligonucleotides (TFOs) is a promising strategy to modulate in vivo gene expression. Triplex formation involving G-rich oligonucleotides as third strand is, however, strongly inhibited by potassium-induced TFO self-association into G-quartet structures. We report here that G-rich TFOs with bulge insertions of (R)-1-O-[4-(1-pyrenylethynyl)-phenylmethyl] glycerol (called twisted intercalating nucleic acids, TINA) show a much lower tendency to aggregate in potassium than wild-type analogues do. We designed purine-motif TINA-TFOs for binding to a regulatory polypurine-polypyrimidine (pur/pyr) motif present in the promoter of the KRAS proto-oncogene. The binding of TINA-TFOs to the KRAS target has been analysed by electrophoresis mobility shift assays and DNase I footprinting experiments. We discovered that in the presence of potassium the wild-type TFOs did not bind to the KRAS target, differently from the TINA analogues, whose binding was observed up to 140 mM KCl. The designed TINA-TFOs were found to abrogate the formation of a DNA-protein complex at the pur/pyr site and to down-regulate the transcription of CAT driven by the murine KRAS promoter. Molecular modelling of the DNA/TINA-TFO triplexes are also reported. This study provides a new and promising approach to create TFOs to target in vivo the genome.

Indexed as

Gene Expression RegulationAnimalsBinding, CompetitiveDNADNA-Binding ProteinsDNA FootprintingDown-RegulationGlycerolGuanineHumansMiceModels, MolecularNIH 3T3 CellsOligonucleotidesPotassiumPromoter Regions, GeneticDNADNA-Binding ProteinsGlycerolGuanineKRAS protein, humanMAS1 protein, humanOligonucleotidesPotassiumProto-Oncogene MasProto-Oncogene ProteinsProto-Oncogene Proteins p21(ras)Pyrenes(R)-1-O-(4-(1-pyrenylethynyl)phenylmethyl)glycerolras Proteinstriplex DNA

Identifiers

PMID18456705
PMCPMC2425464
OpenAlexW1974116446

What OpenQuestion holds

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LicenceCC BY-NC
Read underepoch 390

Registered trials

None linked

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.