Prebiotic Phosphorylation and Concomitant Oligomerization of Deoxynucleosides to form DNA

Abstract

Recent demonstrations of RNA–DNA chimeras (RDNA) enabling RNA and DNA replication, coupled with prebiotic co‐synthesis of deoxyribo‐ and ribo‐nucleotides, have resurrected the hypothesis of co‐emergence of RNA and DNA. As further support, we show that diamidophosphate (DAP) with 2‐aminoimidazole (amido)phosphorylates and oligomerizes deoxynucleosides to form DNA—under conditions similar to those of ribonucleosides. The pyrimidine deoxynucleoside 5′‐O‐amidophosphates are formed in good (≈60 %) yields. Intriguingly, the presence of pyrimidine deoxynucleos(t)ides increased the yields of purine deoxynucleotides (≈20 %). Concomitantly, oligomerization (≈18–31 %) is observed with predominantly 3′,5′‐phosphodiester DNA linkages, and some (<5 %) pyrophosphates. Combined with previous observations of DAP‐mediated chemistries and the constructive role of RDNA chimeras, the results reported here help set the stage for systematic investigation of a systems chemistry approach of RNA–DNA coevolution.

RNA auto-polymerisation from 2’,3’-cyclic nucleotides at air-water interfaces

“…[2][3][4][5][6] Mainly, chemical activation strategies are deployed in polymerisation reactions, 3,7 and template-directed primer extension of sequences rely on ex-situ activation of monomers. 8,9 We base this study on 2´,3´-cyclic mononucleotides (cNMP) which (a) possess an intrinsically activated phosphate; (b) are products of several prebiotic phosphorylation and nucleotide syntheses; [10][11][12][13][14] and (c) are products of neutral to alkaline chemical and enzymatic hydrolyses of RNA. [15][16][17][18][19] In comparison, the dry polymerisation of 3´,5´-cyclic GMP, [20][21][22] did not foster the copolymerisation of the other nucleotides.…”

A physicochemical orthophosphate cycle via a kinetically stable thermodynamically activated intermediate enables mild prebiotic phosphorylations

“…Alternative approaches to prebiotic phosphorylation have exploited activated sources of phosphate. Phosphoramidates, including diamidophosphate (DAP), have been highlighted as powerful prebiotic phosphorylation reagents 17 – 23 . However, a prebiotically relevant method to directly recycle orthophosphate back into DAP has not been demonstrated.…”

Diamidophosphate (DAP): A Plausible Prebiotic Phosphorylating Reagent with a Chem to BioChem Potential?

“…It was found that increased temperature (55 °C) and wet‐dry cycling led to simultaneous formation of (a) oligodeoxynucleotides with predominantly 3′,5′‐phosphodiester linkages and (b) 5′‐polyphosphorylated species – once again pointing to the versatility of DAP to act both as a phosphorylating and activating agent. Interestingly, pyrophosphate‐linked oligonucleotides, which are usually formed in other oligomerization using phosphorimidazolides, were minor components of the reaction products as reported in this work [29] . The mild conditions under which DAP can phosphorylate ribonucleosides to form 2’,3’‐cyclophosphates that are activated towards ring‐opening reaction makes them suitable for ligation reactions.…”

“…reported that the DAP‐mediated phosphorylation chemistry under the paste conditions could be extended to deoxynucleosides as well but required change of the activator from imidazole to 2‐aminoimidazole. [29] The phosphorylation proceeded primarily at the 5′‐position affording the 5’‐amidophosphate nucleotides (Scheme 6 ). Once again, the pyrimidine deoxynucleosides reacted more efficiently than their purine counterparts.…”

“…Interestingly, pyrophosphate‐linked oligonucleotides, which are usually formed in other oligomerization using phosphorimidazolides, were minor components of the reaction products as reported in this work. [29] The mild conditions under which DAP can phosphorylate ribonucleosides to form 2’,3’‐cyclophosphates that are activated towards ring‐opening reaction makes them suitable for ligation reactions.…”