CRC 235 Emergence of Life

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Prolinyl Nucleotides Drive Enzyme-Free Genetic Copying of RNA

F. Welsch 2023 Angew. Chem. Int. Ed.


Franziska Welsch, Eric Kervio, Peter Tremmel, and Clemens Richert

Angew. Chem. Int. Ed.


Proline is one of the proteinogenic amino acids. It isfound in all kingdoms of life. Italsohas remarkable activity as organocatalyst, and it is of structural importance for many folded polypeptides. Here we show that prolinyl nucleotides with a phosphoramidate linkage are active building blocksin enzyme-and ribozyme-free copying of RNA in thepresence of monosubstitutedimidazolesas organocatalysts. Both dinucleotidesand mononucleotidesare incorporated at the terminus of RNA primers in aqueous buffer, as instructed by the template sequence, in up to eightconsecutive extension steps. Our results show thatcondensation products of amino acids and ribonucleotides can act like nucleoside triphosphates in media devoid of enzymes or ribozymes. They are metastable building blocks,readily activated by catalysts, helpingto explain why thecombination of -amino acidsand nucleic acids wasselected in molecular evolution