Synthesis and hybridization properties of an acyclic achiral phosphonate DNA analogue Original Research Article

Protected N-(2-hydroxyethyl)-N-(nucleobase-acetyl)aminomethanephosphonic acids (6a–d) of all four DNA nucleobases have been prepared and oligomerized by solid-phase synthesis. Four DNA decamers containing 1–10 of these ‘PPNA’ monomers were prepared and evaluated by Tm measurements (medium salt) for binding to their DNA and RNA complements. One central modification reduced the binding strongly (ΔTm=−10 °C), but contiguous PPNA monomers gave smaller effects, and the all-PPNA decamer bound to RNA with a ΔTm of −1.2 °C per modification. Thus PPNA oligomers are inferior DNA and RNA binders compared to the closely related and strongly binding PNA oligomers.