Effects of peptide nucleic acids (PNAs) on gene transcription

Peptide nucleic acids (PNAs) have recently been proposed as useful reagents in experiments aimed at the control of gene expression. PNAs backbone consists of N-(2-aminoethyl)-glycine units linked by amide bonds; therefore, these molecules are achiral and neutral, and are extremely efficient in hybridizing with DNA and RNA, generating PNA-DNA and PNA-RNA hybrid molecules exhibiting high stability even at low and medium ionic strength. PNA-mediated effects on in vitro and ex vivo transcription are here reviewed. Enhancing or inhibitory activity of PNAs on gene transcription have been reported to be mainly due to a process which involves strand invasion of target DNA containing homopurine/homopyrimidine stretches with the generation of(PNA)(2)/DNA triplexes. On the contrary, few informations are available on the possible use of PNAs as "decoy" molecules able to interact with DNA-binding proteins, including transcription factors. In this paper we also reviewed results from our laboratory obtained studying the effects of DNA/DNA, DNA/PNA or PNA/PNA molecules mimicking the NF-kB binding sites of the human immunodeficiency type 1 virus (HIV-1) on long terminal repeat (LTR)-driven in vitro transcription. The results herein reported allow to suggest that PNA/PNA molecules and DNA/PNA hybrids are capable to inhibit transcription through different mechanisms of action. The effects of PNAs and PNA/PNA hybrids on transcription are mainly due to strand invasion of target gene sequences. On the contrary, the activity of DNA/PNA on in vitro gene transcription could be due to direct interaction with transcription factors. These results should encourage studies on modified PNAs in older to deter-mine whether PNAs could be designed, synthetized and tested to exhibit a sequence-specific "decoy" activity. For this point of view, chiral PNAs, PHONA (in which the peptide bond is replaced by a phosphonic acid ester bridge) and PNA-DNA chimeras should be considered as potential molecules able to display efficient sequence-specific interactions with target proteins.