New trends for the development of novel decoy molecules against nuclear factor kappa-B (NF-kB) transcription factor

摘要

Transcription factor decoy (TFD) pharmacotherapy against nuclear factor kappa B (NF-kB) proteins appears to be an important strategy for therapy of inflammatory diseases, since NF-kB is deeply involved in the process of inflammation. In this short review, we describe reported data on the effects of peptide nucleic acids (PNAs)-DNA chimeras as TFD molecules. These molecules are composed of a part of PNA and a part of DNA, obey the Watson-Crick rules on binding to complementary DNA and RNA and display water solubility. With respect to TFD approach, promising results have been obtained using double-stranded PNA-DNA chimeras mimicking the NF-kB and Spl binding sites present within the long terminal repeat (LTR) of the human immunodeficiency type 1 virus (HIV-1). In addition, PNA-DNA chimeras are more resistant than DNA/DNA hybrids to nucleases and are suitable for delivery with cationic liposomes and microspheres. In the near future chimeric molecules could be developed with unique features, including terminal removable peptide signals directing internalisation of the decoy molecules to selected target cells and nuclear localization. These engineered molecules could be of great interest in in vivo experiments for development of treatment of human diseases associated with NF-kB activation, including several inflammatory diseases.