N2′→P3′ Phosphoramidate Glycerol Nucleic Acid as a Potential Alternative Genetic System

Glycerol nucleic acid (GNA) is an interesting base-pairing system with an acyclic, three-carbon backbone. In the present study, GNA analogues with N2'-> P3' phosphoramidate linkages (npGNA) have been synthesized and their base-pairing properties examined. Thermal denaturation and circular dichroism studies show that npGNA can form stable duplexes with itself and with GNA. Furthermore, we show that npGNA can be assembled by template-directed ligation of 3'-imidazole-activated-2'-amino GNA dinucleotides. These results suggest that npGNA is a potential candidate for a self-replicating system based upon phosphoramidate linkages.