Synthesis and hybridization properties of an acyclic achiral phosphonate DNA analogue

Abstract

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 T m measurements (medium salt) for binding to their DNA and RNA complements. One central modification reduced the binding strongly ( ΔT m =−10 °C ), but contiguous PPNA monomers gave smaller effects, and the all-PPNA decamer bound to RNA with a ΔT m 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.