Transcription factor decoy molecules based on a peptide nucleic acid (PNA)-DNA chimera mimicking Sp1 binding sites(600 views) Borgatti M, Lampronti I, Romanelli A, Pedone C, Saviano M, Bianchi N, Mischiati C, Gambari R
Keywords: Biochemistry, Molecular Biology, Proteins, Peptides, Nucleic Acids, Cation, Chimeric Protein, Dna Hybrid, Double Stranded Dna, Glycine Derivative, Liposome, N (2 Aminoethyl)glycine, Nuclear Protein, Peptide Nucleic Acid, Pseudopeptide, Transcription Factor Sp1, Unclassified Drug, Hybrid Protein, Oligonucleotide, Article, Binding Affinity, Binding Site, Cell Membrane Resistance, Chemical Structure, Complex Formation, Controlled Study, Dna Dna Hybridization, Dna Strand, Enzyme Degradation, Gene Therapy, Human, Human Cell, Molecular Interaction, Molecular Mimicry, Molecular Stability, Priority Journal, Protein Dna Binding, Protein Structure, Transcription Regulation, Cell Nucleus, Cell Strain K 562, Genetic Transfection, Metabolism, Protein Binding, Protein Tertiary Structure, K562 Cells, Recombinant Fusion Proteins, Sp1 Transcription Factor, Time Factors, N (2 Aminoethyl) Glycine,
Affiliations: *** IBB - CNR ***
Dept. of Biochem./Molecular Biology, Ferrara University, Via L. Borsari n.46, 44100 Ferrara, Italy
Inst. of Biostructure and Bioimaging, CNR, 80134 Napoli, Italy
Biotechnology Centre, Ferrara University, Via Fossato di Mortara 8/A, 44100 Ferrara, Italy
Dept. of Biochem. /Molecular Biology, Ferrara University, Via L. Borsari n. 46, 44100 Ferrara, Italy
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Transcription factor decoy molecules based on a peptide nucleic acid (PNA)-DNA chimera mimicking Sp1 binding sites
Peptide nucleic acids (PNAs) are DNA-mimicking molecules in which the sugar-phosphate backbone is replaced by a pseudopeptide backbone composed of N-(2aminoethyl)glycine units. We determined whether double-stranded molecules 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 molecular 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 theoretically alter the molecular 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 molecules based on PNA-DNA-PNA chimeras are very effective decoy molecules, encouraging further experiments focused on the possible use of these molecules for the development of potential agents for a decoy approach in gene therapy. In this respect, the finding that PDP-based decoy molecules are more resistant than DNA/DNA hybrids to enzymatic degradation 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
Chattopadhyay A, Cogdell R, Crespo-hernandez CE, Datta A, De A, Haacke S, Hariharan M, Helliwell J, Hughes A, Improta R, Jones M, Joseph J, Karsili T, Kohler B, Krishnan R, Kuriakose A, L , M , Markovitsi D, Medhi H, Periyasamy G, Pradeepkumar PI, Roy Chowdhury P, Sarangi M, Schapiro I, Schertler GFX, Schlichting I, Segarra-marti J, Swaminathan R, V , V , Van Grondelle R, Venkatraman RK, Venkatramani R, Watts A * Light induced charge and energy transport in nucleic acids and proteins: general discussion(152 views) Faraday Discuss (ISSN: 1359-6640print, 1359-6640linking), 2018 Apr 1; 207: 153-180. Impact Factor:4.194 ViewExport to BibTeXExport to EndNote
Chandra A, Cogdell R, Crespo-hernandez CE, Datta A, Giussani A, Haacke S, Helliwell J, Improta R, Jayasree RS, Jones M, Karsili T, Kohler B, L , M , Mandal I, Markovitsi D, Medhi H, Mishra PP, Pradeepkumar PI, Roy Chowdhury P, Sarangi M, Schapiro I, Schlichting I, Segarra-marti J, Sharma A, V , V , Van Grondelle R, Watts A * Light induced damage and repair in nucleic acids and proteins: general discussion(136 views) Faraday Discuss (ISSN: 1359-6640print, 1359-6640linking), 2018 Apr 1; 207: 389-408. Impact Factor:4.194 ViewExport to BibTeXExport to EndNote
Bhat V, Cogdell R, Crespo-hernández CE, Datta A, De A, Haacke S, Helliwell J, Improta R, Joseph J, Karsili T, Kohler B, Krishnan R, Mahil LM, Lewis F, Mandal I, Markovitsi D, Mishra PP, Paul S, Periyasamy G, Pradeepkumar PI, Roy Chowdhury P, Sarangi M, Sasikumar D, Schapiro I, Schertler GFX, Schlichting I, Segarra-martí J, Swaminathan R, Vishnu V, Van Grondelle R, Varghese R, Venkatramani R * Photocrosslinking between nucleic acids and proteins: general discussion(146 views) Faraday Discussions, 2018; N/D: N/D-N/D. Impact Factor:3.427 ViewExport to BibTeXExport to EndNote