The chemistry of peptide nucleic acids

Peptide Nucleic Acids (PNA) are oligonucleotide analogues in which the sugar-phosphate backbone has been replaced by a polyamidic chain. They were shown to bind to complementary DNA and RNA sequences with high affinity and selectivity. For these reasons, they have become very popular, as tools in molecular biology and biotechnology, as diagnostic agents, and as potential antisense drugs. The synthesis of PNA monomers has been described with different strategies using different protecting groups for the amino function (Boc, Fmoc, or Mmt) and for the nucleobases. Strategies for oligomerization, either by homogeneous or by solid-phase synthesis, have been reported. A large number of modified PNAs have also been envisaged. The present work provides a general overview of the different PNA backbones and of modified nucleobases, with special regard to the synthetic strategies used. The occurrence of racemization during the synthesis of chiral PNA analogues is also discussed. PNA/DNA duplexes are formed obeying the usual Watson-Crick rules, as well as (PNA)(2)/DNA triplexes with homopyrimidine PNAs in low ionic strength solutions. The thermal stability of these adducts is described. In particular, the influence of PNA structure modification and chirality on the binding affinity and selectivity are discussed.