Synthesis of N3′-P5′-linked Phosphoramidate DNA by Nonenzymatic Template-Directed Primer Extension

A fast and accurate pathway for nonenzymatic RNA replication would simplify models for the emergence of the RNA world from the prebiotic chemistry of the early earth. However, numerous difficulties stand in the way of an experimental demonstration of effective nonenzymatic RNA replication. To gain insight into the necessary properties of potentially self-replicating informational polymers, we have studied several model systems based on amino–sugar nucleotides. Here we describe the synthesis of N3′–P5′-linked phosphoramidate DNA (3′-NP-DNA) by the template-directed polymerization of activated 3′-amino-2′,3′-dideoxyribonucleotides. 3′-NP-DNA is an interesting model because of its very RNA-like A-type duplex conformation and because activated 3′-amino-2′,3′-dideoxyribonucleotides are much more reactive than the corresponding activated ribonucleotides. In contrast to our previous studies with 2′-amino-2′,3′-dideoxyribonucleotides (for which G and C but not A and T exhibit efficient template copying), we have ...