Transplatin-conjugated triplex-forming oligonucleotides form adducts with both strands of DNA

Meghan A. Campbell, Paul S. Miller

Research output: Contribution to journalArticlepeer-review

9 Scopus citations


Triplex-forming oligonucleotides (TFOs) can bind to polypurine • polypyrimidine tracts in DNA and, as a consequence, perturb the normal functioning of a targeted gene. The effectiveness of such antigene TFOs can potentially be enhanced by covalent attachment of the TFO to its DNA target. Here, we report that attachment of N-7-platinated guanine nucleosides to the 3′- and/or 5′-ends of oligopyrimidine TFOs enables these TFOs to form highly stable adducts with target DNA deoxyguanosines or deoxyadenosines that are adjacent to the TFO binding site. Such adduct formation stably anchors the TFO to its target. Depending on the sequences adjacent to the TFO binding site, adduct formation can occur on either strand of the DNA. Adduct formation by 3′,5′-bis-platinated TFOs can result in the formation of an interstrand cross-link between both strands of the DNA duplex. Formation of the adducts, which could be reversed by treatment with sodium cyanide, was dependent upon the ability of the TFO to bind to DNA and appeared to occur at a rate slower than that at which the TFO bound to the DNA duplex. The extent of adduct formation at 37°C by platinated deoxyribo-TFOs diminished as the pH was increased from 6.5 to 7.4. In contrast, high levels (∼86%) of adduct formation by platinated 2′-O-methylribo-TFOs were observed at both pH 6.5 and pH 7.4. Platinated 2′-O-methylribo-TFOs were also shown to bind to plasmid DNA and inhibit transcription in vitro, and to inhibit plasmid replication in E. coli cells. These results suggest that platinum-conjugated TFOs may be good candidates for use as antigene agents.

Original languageEnglish (US)
Pages (from-to)2222-2230
Number of pages9
JournalBioconjugate Chemistry
Issue number12
StatePublished - Dec 16 2009
Externally publishedYes

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Biomedical Engineering
  • Pharmacology
  • Pharmaceutical Science
  • Organic Chemistry


Dive into the research topics of 'Transplatin-conjugated triplex-forming oligonucleotides form adducts with both strands of DNA'. Together they form a unique fingerprint.

Cite this