Positively charged oligonucleotides overcome potassium-mediated inhibition of triplex DNA formation

J M Dagle; D L Weeks

doi:10.1093/nar/24.11.2143

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Positively charged oligonucleotides overcome potassium-mediated inhibition of triplex DNA formation

Journal article

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Peer reviewed

Positively charged oligonucleotides overcome potassium-mediated inhibition of triplex DNA formation

J M Dagle and D L Weeks

Nucleic acids research, Vol.24(11), pp.2143-2149

06/01/1996

DOI: 10.1093/nar/24.11.2143

PMCID: PMC145908

PMID: 8668547

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Abstract

The formation of triplex DNA using unmodified, purine-rich oligonucleotides (ODNs) is inhibited by physiologic levels of potassium. Changing negative phosphodiester bonds in a triplex forming oligonucleotide (TFO) to neutral linkages causes a small increase in triplex formation. When phosphodiester bonds in a TFO are converted to positively-charged linkages the formation of triplex DNA increases dramatically. In the absence of KCl, a 17mer TFO containing 11 positively-charged linkages at a concentration of 0.2 microM converts essentially all of a 30 bp target duplex to a triplex. Less than 15% of the target duplex is shifted by 2 microMolar of the unmodified TFO. In 130 mM KCl, triplex formation is undetectable using the unmodified TFO, while triplex formation is nearly complete with 2 microM positively-charged TFO. With increasing potassium, TFOs containing a higher proportion of modified linkages show enhanced triplex formation compared with those less modified. In contrast with unmodified TFOs, triplex formation with more heavily modified TFOs can occur in the absence of divalent cations. We conclude that replacement of phosphodiester bonds with positively-charged phosphoramidate linkages results in more efficient triplex formation, suggesting that these compounds may prove useful for in vivo applications.

Details

Title: Subtitle: Positively charged oligonucleotides overcome potassium-mediated inhibition of triplex DNA formation
Creators: J M Dagle - Department of Pediatrics, The University of Iowa, Iowa City 52242, USA
D L Weeks - Department of Pediatrics, The University of Iowa, Iowa City 52242, USA
Resource Type: Journal article
Publication Details: Nucleic acids research, Vol.24(11), pp.2143-2149
DOI: 10.1093/nar/24.11.2143
PMID: 8668547
PMCID: PMC145908
NLM abbreviation: Nucleic Acids Res
ISSN: 0305-1048
eISSN: 1362-4962
Language: English
Date published: 06/01/1996
Academic Unit: Stead Family Department of Pediatrics; Epidemiology; Biochemistry and Molecular Biology; Neonatology
Record Identifier: 9984025249702771

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