Synthesis, properties and functions of peptide nucleic acids (PNA) and their derivatives

Abstract

In 1991 Nielsen et al. first described peptide nucleic acid (PNA), which is a DNA mimic with a pseudopeptide backbone composed of N-(2-aminoethyl)glycine units with the nucleobases attached to the glycine nitrogen via carbonyl methylene linkers. PNA is a very attractive molecule as a DNA mimic because it shows high biological stability with strong binding-affinity to complementary DNA and RNA. The limitations of PNA include low aqueous solubility, ambiguity in DNA binding orientation and poor membrane permeability. Various PNA derivatives were reported to improve physicochemical and biological properties of PNA. Chirality was introduced into the achiral PNA backbone to influence the selectivity in DNA binding orientation. PNA backbone was rigidified by introduction of ring structure to preorganize PNA for duplex formation. This review focuses on the chemistry and biological activity of PNA, and gives an overview of backbone modifications of PNA.