Synthesis and hybridization properties of an acyclic achiral phosphonate DNA analogue

Protected N-(2-hydroxyethyl)-N-(nucleobase-acetyl) 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 (Delta T-m = -10 degrees C), but contiguous PPNA monomers gave smaller effects, and the all-PPNA decamer bound to RNA with a Delta T-m of -1.2 degrees C per modification. Thus PPNA oligomers are inferior DNA and RNA binders compared to the closely related and strongly binding PNA oligomers. (C) 1998 Elsevier Science Ltd. All rights reserved.