Skip to main content

Biological Activity and Delivery of Peptide Nucleic Acids (PNA)-DNA Chimeras for Transcription Factor Decoy (TFD) Pharmacotherapy

Buy Article:

$63.00 plus tax (Refund Policy)

Abstract:

Peptide nucleic acids (PNAs) are recently described DNA mimics, in which the sugar-phosphate backbone is replaced by N-(2-aminoethyl)glycine units. These molecules efficiently hybridize with complementary DNA, forming Watson-Crick double helices. In addition, the interest of PNAs and PNA-based analogs is related to the fact that they are resistant to DNases and proteinases. While applications of PNAs as antisense and antigéne molecules in non-viral gene therapy are well documented, their effects as potential transcription factor decoy (TFD) molecules is not demonstrated. PNA / PNA and PNA / DNA duplex are not suitable for TFD. In fact, PNA / PNA duplex does not recognize transcription factors, while, in the case of PNA / DNA hybrids containing nuclear factor binding sites, the interaction with transcription factors is unstable. By sharp contrast, double stranded molecules based on PNADNA chimeras exhibit strong TFD activity, display enzymatic stability in serum and cellular extracts and can be delivered to target cells after complexation with liposomes and microspheres. The TFD molecules based on PNA-DNA chimeras can be further engineered by addition of short peptides facilitating cell penetration and nuclear localization. Therefore, these engineered molecules could be of great interest for in vivo experiments on non-viral gene therapy of a variety of diseases, including neoplastic and viral diseases, for which the TFD approach has been already demonstrated as a very useful strategy.

Keywords: decoy; delivery; gene therapy; peptide-nucleic acids; pna-dna chimeras; transcription

Document Type: Review Article

DOI: http://dx.doi.org/10.2174/0929867043365242

Affiliations: Department of Biochemistry and Molecular Biology, Via Luigi Borsari, 46, 44100 - Ferrara - Italy.

Publication date: May 1, 2004

More about this publication?
  • Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews written by leaders in the field covering a range of the current topics in medicinal chemistry. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.
ben/cmc/2004/00000011/00000010/art00003
dcterms_title,dcterms_description,pub_keyword
6
5
20
40
5

Access Key

Free Content
Free content
New Content
New content
Open Access Content
Open access content
Subscribed Content
Subscribed content
Free Trial Content
Free trial content
Cookie Policy
X
Cookie Policy
ingentaconnect website makes use of cookies so as to keep track of data that you have filled in. I am Happy with this Find out more