Peptide-nucleic acids (PNAs): A tool for the development of gene expression modifiers

Peptide nucleic acids (PNAs) represent nucleic acid analogues with unique b iochemical properties and of great interest for the development of therapeu tic agents. The firstly designed and tested PNAs are molecules in which the sugar-phosphate backbone of DNA was replaced with a pseudopeptide chain co nstituted by N-(2-aminoethyl) glycine monomers. Nucleobases can be linked t o this backbone through a carboxymethyl moiety, which allows to maintain a two atom spacer between the backbone and the bases. Since the first reports on PNAs based on N-(2-aminoethyl) glycine backbone, other PNA analogues ha ve been synthesized, with the main purpose of improve biological activities as well as stability and efficient delivery to target cells. Of great inte rest are chiral PNAs, PNA analogues bearing phosphate groups (PHONA), PNA-D NA and PNA-peptide chimeras, PNA linked to non-peptide vectors. PNAs hybrid ize to DNA and RNA with high efficiency following the Watson-Crick hybridiz ation rules, forming highly stable PNA/DNA and PNA/RNA duplexes. In additio n, homopyrimidine PNAs, as well as PNAs containing a high pyrimidine:purine ratio, are able to bind to DNA or RNA forming highly stable (PNA)(2)-DNA t riple helices. Accordingly, therapeutic PNA and PNA analogues could act as antigene as well as antisense molecules. In addition, recent studies provid e evidences for the possible use of PNA-based therapeutic molecules as arti ficial promoters, as decoy or ribozyme facilitator. Among the therapeutic a pplications of PNA-based molecules, the most pomising include anti-cancer a nd anti-viral experimental strategies, but activity of PNAs against bacteri a and medically important parasitic organisms have been also reported.