DNA-catalyzed reactivity of a phosphoramidate functional group and formation of an unusual pyrophosphoramidate linkage

During in vitro selection for DNA-catalyzed lysine reactivity, we identified a deoxyribozyme that instead catalyzes nucleophilic attack of a phosphoramidate functional group at a 5′-triphosphate-RNA, forming an unusual pyrophosphoramidate (N-P ^V-O-P ^V) linkage. This finding highlights the relatively poor nucleophilicity of nitrogen using nucleic acid catalysts, indicating a major challenge for future experimental investigation.