Abstract
A pair of decameric pseudocomplementary PNAs which bind to their mixed purine-pyrimidine sequence target in duplex DNA by double duplex invasion has been synthesized with a derivative of 8-methoxypsoralen conjugated to one of the PNAs. It is shown that this pair of psoralen-conjugated pseudocomplementary PNA oligomers, which target a site in the pBluescriptKS+ vector, upon irradiation with long-wavelength UV light (UVA) with high efficiency and specificity form photoadducts to an adjacent 5'-TA site, and more than 50% of these adducts are DNA interstrand cross-links. Transcription elongation by T7 or T3 RNA polymerase is specifically arrested at the psoralen cross-linking site, yielding more than 90% arrested product. These results emphasize the potential of pseudocomplementary PNA oligomers for highly specific gene targeting, in particular, with respect to sequence-directed psoralen photomodification of double-stranded DNA. Thus, such psoralen-PNA conjugates could be very useful in a range of biology and drug discovery applications.
| Original language | English |
|---|---|
| Journal | Bioconjugate Chemistry |
| Volume | 18 |
| Issue number | 2 |
| Pages (from-to) | 567-72 |
| Number of pages | 6 |
| ISSN | 1043-1802 |
| DOIs | |
| Publication status | Published - 30 Jan 2007 |
Keywords
- Cross-Linking Reagents/chemistry
- DNA/chemistry
- DNA-Directed RNA Polymerases
- Electrophoretic Mobility Shift Assay
- Ficusin/chemistry
- Gene Targeting
- Nucleic Acid Conformation
- Nucleic Acid Heteroduplexes/chemistry
- Peptide Nucleic Acids/chemistry
- Ultraviolet Rays