| Abstract
| - A pair of decameric pseudocomplementary PNAs which bind to their mixed purine−pyrimidine sequence targetin duplex DNA by double duplex invasion has been synthesized with a derivative of 8-methoxypsoralen conjugatedto 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) withhigh efficiency and specificity form photoadducts to an adjacent 5‘-TA site, and more than 50% of these adductsare DNA interstrand cross-links. Transcription elongation by T7 or T3 RNA polymerase is specifically arrestedat the psoralen cross-linking site, yielding more than 90% arrested product. These results emphasize the potentialof 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 bevery useful in a range of biology and drug discovery applications.
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