Resistance of Decoy PNA-DNA Chimeras to Enzymatic Degradation in Cellular Extracts and Serum
Articolo
Data di Pubblicazione:
2003
Citazione:
Resistance of Decoy PNA-DNA Chimeras to Enzymatic Degradation in Cellular Extracts and Serum / M. Borgatti, A. Romanelli, M. Saviano, C. Pedone, I. Lampronti, L. Breda, C. Nastruzzi, N. Bianchi, C. Mischiati, R. Gambari. - In: ONCOLOGY RESEARCH. - ISSN 0965-0407. - 13:5(2003), pp. 279-287. [10.3727/096504003108748339]
Abstract:
Double-stranded molecules based on peptide nucleic acids (PNAs)-DNA chimeras carrying binding sites for known transcription factors could be of great interest in decoy pharmacotherapy of neoplastic diseases. For instance, decoy molecules recognizing Sp1 and NF-κB transcription factors were found to inhibit tumor cell growth and invasion activity. In this respect, we have recently found that double-stranded PNA-DNA chimeras carrying NF-κB binding sites inhibit the binding of NF-κB p52 and p50 transcription factors to target DNA molecules. In this article we determined the resistance of double-stranded decoy molecules based on PNA-DNA chimeras to exonucleases (both 3â²â5â² and 5â²â3â² exonucleases), endonucleases, and 5â²-phosphatases. In addition, we performed experiments aimed at determining the resistance of these molecules in cellular extracts and serum. Finally, we used liposomes as protective agents in experimental conditions in which the decoy molecules employed were found to be unstable (high concentrations of enzymes, cellular extracts, or serum). The results obtained demonstrated that decoy molecules based on PNA-DNA chimeras are more resistant than DNA-based decoys to exo- and endonucleases, serum, and cellular extracts. In addition, the resistance of DNA/PNA hybrids in the presence of high concentrations of serum and cellular extracts was increased after complexation to cationic liposomes, due to the fact that double-stranded PNA-DNA-PNA chimeras bind to these delivery systems. The results obtained in the present study support the proposal of molecules based on PNA-DNA chimeras for an efficient decoy treatment of tumor cells both in vitro and in vivo.
Tipologia IRIS:
01 - Articolo su periodico
Keywords:
peptide nucleic acid (PNA); peptide nucleic acid (PNA)-DNA chimeras; decoy
Elenco autori:
M. Borgatti, A. Romanelli, M. Saviano, C. Pedone, I. Lampronti, L. Breda, C. Nastruzzi, N. Bianchi, C. Mischiati, R. Gambari
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