PNA-nucleic acid complexes. Structure, stability and dynamics

Growing interest in gene targeting drugs has inspired the development of a multitude of nucleic acid analogues, many of which feature substitutions in the phosphodiester moiety of the backbone (reviewed by Mesmaeker et al . 1995 and Nielsen, 1995). Peptide nucleic acid (PNA) is an example of a more radical redesign of DNA. The entire sugar-phosphate backbone is substituted by a chain of peptide-like N-(2-aminoethyl)glycine units so that an achiral and uncharged DNA-mimic is obtained (Fig. 1; Nielsen et al . 1991). The synthesis is based on standard peptide chemistry (Christensen et al . 1995) and has been automated. PNA can relatively easily be modified to include modifications of the backbone as well as of the bases (Hyrup & Nielsen, 1996). PNA is chemically stable and, in contrast to natural nucleic acids and peptides, PNA is expected to remain intact in living cells since it is not a substrate for natural hydrolytic enzymes and is not degraded by cell extracts (Demidov et al . 1994).