Acid‐Catalyzed RNA‐Oligomerization from 3’,5’‐cGMP

Abstract

The assembly of ancient informational polymers from nucleotide precursors is the central challenge of life's origin on our planet. Among the possible solutions, dry polymerization of 3’,5’‐cyclic guanosine monophosphate (3’,5’‐cGMP) has been proposed as a candidate to create oligonucleotides of 15–20 units in length. However, the reported sensitivity of the reaction to the presence of cations raised questions of whether this chemistry could be relevant in a geological context. The experiments in this study show that the presence of cations is not restrictive as long as the reaction is conducted in an acidic environment, in contrast to previous reports that suggested optimal conditions at pH 9.

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

“…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. 22 We found that 2´,3´-cGMP polymerised spontaneously under alkaline (pH [7][8][9][10][11][12], drying conditions (40-80 °C).…”

“…[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. 22 We found that 2´,3´-cGMP polymerised spontaneously under alkaline (pH [7][8][9][10][11][12], drying conditions (40-80 °C). The other canonical cNMP were relatively inert under similar conditions.…”

“…Based on the stack-assisted polymerisation of 3´,5´ cGMP, 22 we studied the suitability of intercalated stack arrangements for the polymerisation of 2´,3´-cNMP. We explored the stability of the stack arrangements, and the incorporation of cNMP monomers into polymerised cGMP scaffold, based on minimum energy structures and molecular dynamics simulations (Figure 4a-c and the computation section, page 58, SI).…”

RNA polymerisation without catalyst from 2’,3’-cyclic nucleotides by drying at air-water interfaces

“…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; [14][15][16][17][18] and (c) are products of neutral to alkaline chemical and enzymatic hydrolyses of RNA. [19][20][21][22][23] In comparison, the dry polymerisation of 3´,5´-cGMP [24][25][26] did not foster the polymerisation of the other ribonucleotides. [26] Orgel and coworkers, reported conditions for 2´,3´-cAMP polymerisation by drying for 40 days with a 5-fold excess of ethane-1,2-diamine and yields up to 0.67% of 14-mers.…”

“…[19][20][21][22][23] In comparison, the dry polymerisation of 3´,5´-cGMP [24][25][26] did not foster the polymerisation of the other ribonucleotides. [26] Orgel and coworkers, reported conditions for 2´,3´-cAMP polymerisation by drying for 40 days with a 5-fold excess of ethane-1,2-diamine and yields up to 0.67% of 14-mers. [4,6] Other catalysts such as imidazole or urea required temperatures up to 85°C and offered lower yields.…”