PNA HYBRIDIZES TO COMPLEMENTARY OLIGONUCLEOTIDES OBEYING THE WATSON-CRICK HYDROGEN-BONDING RULES

DNA ANALOGUES are currently being intensely investigated owing to thei r potential as gene-targeted drugs1-3. Furthermore, their properties a nd interaction with DNA and RNA could provide a better understanding o f the structural features of natural DNA that determine its unique che mical, biological and genetic properties3,4. We recently designed a DN A analogue, PNA, in which the backbone is structurally homomorphous wi th the deoxyribose backbone and consists of N-(2-aminoethyl)glycine un its to which the nucleobases are attached5-9. We showed that PNA oligo mers containing solely thymine and cytosine can hybridize to complemen tary oligonucleotides, presumably by forming Watson-Crick-Hoogsteen (P NA)2-DNA triplexes, which are much more stable than the corresponding DNA-DNA duplexes5-7, and bind to double-stranded DNA by strand displac ement5,8. We report here that PNA containing all four natural nucleoba ses hybridizes to complementary oligonucleotides obeying the Watson-Cr ick base-pairing rules, and thus is a true DNA mimic in terms of base- pair recognition.