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bioRxiv · 10.1101/2022.01.25.477680

Potentially prebiotic synthesis of aminoacyl-RNA via a bridging phosphoramidate-ester intermediate

Roberts, S. J.·Liu, Z.·Sutherland, J. D.
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Abstract

Translation according to the genetic code is made possible by selectivity both in aminoacylation of tRNA and in anticodon:codon recognition. In extant biology, tRNAs are selectively aminoacylated by enzymes using high-energy intermediates, but how this might have been achieved prior to the advent of protein synthesis has been a largely unanswered question in prebiotic chemistry. We have now elucidated a novel, prebiotically plausible stereoselective aminoacyl-RNA synthesis which starts from RNA-amino acid phosphoramidates and proceeds via phosphoramidate-ester intermediates which subsequently undergo conversion to aminoacyl-esters by mild acid hydrolysis. The chemistry avoids the intermediacy of high-energy mixed carboxy-phosphate anhydrides and is greatly favored under eutectic conditions, which also potentially allow for the requisite pH fluctuation through the variable solubility of CO2 in solid/liquid water.

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Roberts, S. J., Liu, Z., Sutherland, J. D.. 2022-01-25. Potentially prebiotic synthesis of aminoacyl-RNA via a bridging phosphoramidate-ester intermediate. https://doi.org/10.1101/2022.01.25.477680

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