PNA hybridizes to complementary oligonucleotides obeying the Watson–Crick hydrogen-bonding rules

Abstract

DNA ANALOGUES are currently being intensely investigated owing to their potential as gene-targeted drugs^1–3. Furthermore, their properties and interaction with DNA and RNA could provide a better understanding of the structural features of natural DNA that determine its unique chemical, biological and genetic properties^3,4. We recently designed a DNA analogue, PNA, in which the backbone is structurally homomorphous with the deoxyribose backbone and consists of N-(2-aminoethyl)glycine units to which the nucleobases are attached^5–9. We showed that PNA oligomers containing solely thymine and cytosine can hybridize to complementary oligonucleotides, presumably by forming Watson–Crick–Hoogsteen (PNA)₂–DNA triplexes, which are much more stable than the corresponding DNA–DNA duplexes^5–7, and bind to double-stranded DNA by strand displacement^5,8. We report here that PNA containing all four natural nucleobases hybridizes to complementary oligonucleotides obeying the Watson–Crick base-pairing rules, and thus is a true DNA mimic in terms of base-pair recognition.