Prolinyl Nucleotides Drive Enzyme‐Free Genetic Copying of RNA
Open accessAbstract
Proline is one of the proteinogenic amino acids. It is found in all kingdoms of life. It also has remarkable activity as an organocatalyst and is of structural importance in many folded polypeptides. Here, we show that prolinyl nucleotides with a phosphoramidate linkage are active building blocks in enzyme‐ and ribozyme‐free copying of RNA in the presence of monosubstituted imidazoles as organocatalysts. Both dinucleotides and mononucleotides are incorporated at the terminus of RNA primers in aqueous buffer, as instructed by the template sequence, in up to eight consecutive extension steps. Our results show that condensation products of amino acids and ribonucleotides can act like nucleoside triphosphates in media devoid of enzymes or ribozymes. Prolinyl nucleotides are metastable building blocks, readily activated by catalysts, helping to explain why the combination of α‐amino acids and nucleic acids was selected in molecular evolution.
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Primer extension reactions have already been analyzed using MALDI.
“It should be noted that MALDI is routinely used in clinical chemistry56 and primer extension reactions have already been analyzed using this technique.57”
From Sequencing of <scp>d</scp>/<scp>l</scp>-DNA and XNA by Templated-Synthesis (2025) · cites this paper as [57]
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- Authors
- Welsch, F., Kervio, E., Tremmel, P., & Richert, C.
- Affiliations
- University of Stuttgart (DE)
- Corresponding author
- Richert, Clemens
- Venue
- Angewandte Chemie International Edition
- Publisher
- Wiley
- Published
- 2023-07-11
- Volume
- 62
- Issue
- 41
- Pages
- e202307591-e202307591
- ISSN
- 1433-7851 (ISSN-L)
- 1521-3773
- OpenAlex
- W4382502674
- Cited by
- 13
- References
- 38
- Citations by year
- 2025: 9 · 2024: 4
- FWCI
- 1.51
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Angewandte Chemie International Edition (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- OPUS Publication Server of the University of Stuttgart (University of Stuttgart) (submittedVersion, cc-by-nc)
- Universitätsbibliothek Stuttgart
- Funders
- Deutsche Forschungsgemeinschaft
- Topics
- Physical Sciences › Physics and Astronomy › Astronomy and Astrophysics › Origins and Evolution of Life
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA and Nucleic Acid Chemistry
- Keywords
- RNA primers, organocatalysis, imidazole catalyst, phosphoramidate linkage, origin of life, prebiotic chemistry, template synthesis
- MeSH terms
- Amino Acids, Nucleic Acids, Nucleotides, RNA, Templates, Genetic, RNA, Catalytic
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