Prebiotic synthesis and triphosphorylation of 3'-amino-TNA nucleosides.

Publisher: Nature Pub. Group Country of Publication: England NLM ID: 101499734 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1755-4349 (Electronic) Linking ISSN: 17554330 NLM ISO Abbreviation: Nat Chem Subsets: MEDLINE

Original Publication: London : Nature Pub. Group

Nucleic Acids* ; Nucleosides*; Base Pairing ; Water

Nucleosides are essential to the emergence of life, and so their synthesis is a key challenge for prebiotic chemistry. Although amino-nucleosides have enhanced reactivity in water compared with ribonucleosides, they are assumed to be prebiotically irrelevant due to perceived difficulties with their selective formation. Here we demonstrate that 3'-amino-TNA nucleosides (TNA, threose nucleic acid) are formed diastereoselectively and regiospecifically from prebiotic feedstocks in four high-yielding steps. Phosphate provides an unexpected resolution, leading to spontaneous purification of the genetically relevant threo-isomer. Furthermore, 3'-amino-TNA nucleosides are shown to be phosphorylated directly in water, under mild conditions with cyclic trimetaphosphate, forming a nucleoside triphosphate (NTP) in a manner not feasible for canonical nucleosides. Our results suggest 3'-amino-TNA nucleosides may have been present on the early Earth, and the ease with which these NTPs form, alongside the inherent selectivity for the Watson-Crick base-pairing threo-monomer, warrants further study of the role they could play during the emergence of life.
(© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Comment in: Nat Chem. 2022 Jul;14(7):725-727. (PMID: 35778560)

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0 (Nucleic Acids)
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059QF0KO0R (Water)

Date Created: 20220701 Date Completed: 20220707 Latest Revision: 20221023

20231215

10.1038/s41557-022-00982-5

35778563