Peptide nucleic acid-DNA decoy chimeras targeting NF-κB transcription factors: Induction of apoptosis in human primary osteoclasts

  • Authors:
    • Letizia Penolazzi
    • Monica Borgatti
    • Elisabetta Lambertini
    • Carlo Mischiati
    • Alessia Finotti
    • Alessandra Romanelli
    • Michele Saviano
    • Carlo Pedone
    • Roberta Piva
    • Roberto Gambari
  • View Affiliations

  • Published online on: August 1, 2004     https://doi.org/10.3892/ijmm.14.2.145
  • Pages: 145-152
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Abstract

Peptide nucleic acids (PNAs) are DNA mimics constituted by a pseudopeptide backbone composed of N-(2-aminoethyl)glycine units. PNAs hybridize with high affinity to complementary sequences of single-stranded RNA and DNA, forming Watson-Crick double helices and are resistant to both nucleases and proteases. While applications of PNAs as antisense and antigene molecules have been described, PNA/DNA and PNA/PNA hybrids are not useful for transcription factor decoy (TFD) pharmacotherapy. By contrast, PNA-DNA-PNA (PDP) chimeras, constituted of sequential PNA, DNA and PNA stretches, are potent decoy molecules in vitro. Interestingly, PDP-based decoys a) are more soluble than PNAs, b) are more resistant than synthetic oligonucleotides to enzymatic activity present in cellular extracts and serum and c) can be delivered with liposomes. In the present study we demonstrated that double-stranded PNA-DNA-PNA chimeras targeting NF-κB transcription factors induce apoptosis of human primary osteoclasts. Our data suggest that PDP-based induction of osteoclast apoptosis could be a therapeutic approach for disorders in which bone resorption is inappropriately excessive.

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August 2004
Volume 14 Issue 2

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Penolazzi L, Borgatti M, Lambertini E, Mischiati C, Finotti A, Romanelli A, Saviano M, Pedone C, Piva R, Gambari R, Gambari R, et al: Peptide nucleic acid-DNA decoy chimeras targeting NF-κB transcription factors: Induction of apoptosis in human primary osteoclasts. Int J Mol Med 14: 145-152, 2004.
APA
Penolazzi, L., Borgatti, M., Lambertini, E., Mischiati, C., Finotti, A., Romanelli, A. ... Gambari, R. (2004). Peptide nucleic acid-DNA decoy chimeras targeting NF-κB transcription factors: Induction of apoptosis in human primary osteoclasts. International Journal of Molecular Medicine, 14, 145-152. https://doi.org/10.3892/ijmm.14.2.145
MLA
Penolazzi, L., Borgatti, M., Lambertini, E., Mischiati, C., Finotti, A., Romanelli, A., Saviano, M., Pedone, C., Piva, R., Gambari, R."Peptide nucleic acid-DNA decoy chimeras targeting NF-κB transcription factors: Induction of apoptosis in human primary osteoclasts". International Journal of Molecular Medicine 14.2 (2004): 145-152.
Chicago
Penolazzi, L., Borgatti, M., Lambertini, E., Mischiati, C., Finotti, A., Romanelli, A., Saviano, M., Pedone, C., Piva, R., Gambari, R."Peptide nucleic acid-DNA decoy chimeras targeting NF-κB transcription factors: Induction of apoptosis in human primary osteoclasts". International Journal of Molecular Medicine 14, no. 2 (2004): 145-152. https://doi.org/10.3892/ijmm.14.2.145