Peptide nucleic acids (PNAs) are DNA-mimicking mols. in which the sugar-phosphate backbone is replaced by a pseudopeptide backbone composed of N-(2-aminoethyl)glycine units. We detd. whether double-stranded mols. based on PNAs and PNA-DNA-PNA (PDP) chimeras could be capable of stable interactions with nuclear proteins belonging to the Sp1 transcription factor family and therefore could act as decoy reagents able to inhibit mol. interactions between Sp1 and DNA. Since the structure of PNA/PNA hybrids is very different from that of the DNA/DNA double helix, they could theor. alter the mol. structure of the double-stranded PNA-DNA-PNA chimeras, perturbing interactions with specific transcription factors. We found that PNA-based hybrids do not inhibit Sp1/DNA interactions. In contrast, hybrid mols. based on PNA-DNA-PNA chimeras are very effective decoy mols., encouraging further expts. focused on the possible use of these mols. for the development of potential agents for a decoy approach in gene therapy. In this respect, the finding that PDP-based decoy mols. are more resistant than DNA/DNA hybrids to enzymic degrdn. appears to be of great interest. Furthermore, their resistance can even be improved after complexation with cationic liposomes to which PDP/PDP chimeras are able to bind by virtue of their internal DNA structure.
Transcription Factor Decoy Molecules Based on a Peptide Nucleic Acid (PNA)-DNA Chimera Mimicking Sp1 Binding Sites
Saviano Michele;
2003
Abstract
Peptide nucleic acids (PNAs) are DNA-mimicking mols. in which the sugar-phosphate backbone is replaced by a pseudopeptide backbone composed of N-(2-aminoethyl)glycine units. We detd. whether double-stranded mols. based on PNAs and PNA-DNA-PNA (PDP) chimeras could be capable of stable interactions with nuclear proteins belonging to the Sp1 transcription factor family and therefore could act as decoy reagents able to inhibit mol. interactions between Sp1 and DNA. Since the structure of PNA/PNA hybrids is very different from that of the DNA/DNA double helix, they could theor. alter the mol. structure of the double-stranded PNA-DNA-PNA chimeras, perturbing interactions with specific transcription factors. We found that PNA-based hybrids do not inhibit Sp1/DNA interactions. In contrast, hybrid mols. based on PNA-DNA-PNA chimeras are very effective decoy mols., encouraging further expts. focused on the possible use of these mols. for the development of potential agents for a decoy approach in gene therapy. In this respect, the finding that PDP-based decoy mols. are more resistant than DNA/DNA hybrids to enzymic degrdn. appears to be of great interest. Furthermore, their resistance can even be improved after complexation with cationic liposomes to which PDP/PDP chimeras are able to bind by virtue of their internal DNA structure.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
