Peptide nucleic acids (PNA). Oligonucleotide analogs with an achiral peptide backbone

Oligonucleotides that specifically recognize messenger RNA or double-stranded DNA present unique opportunities for inhibiting protein synthesis (the antisense approach) or for modulating gene expression, e.g., via triple helix formation. The deoxyribose phosphate backbone of DNA has been modified in a number of ways to increase nuclease stability and cell membrane permeability, assuming that major changes would be deleterious to the "DNA hybridization properties". Consequently, derivatives such as mono- or dithiophosphates, methyl phosphonates, borano phosphates, etc., as well as formacetal, carbamate, and siloxane, or dimethylenethio-, -sulfoxido-, and -sulfono-linked, species were prepared. The synthesis of peptides is more versatile than oligonucleotide synthesis, allowing the facile design of an achiral backbone and relatively large-scale production. We therefore designed peptide nucleic acids (PNA), i.e., molecules where the individual nucleobases were linked to an achiral peptide backbone.