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Prebiotically plausible oligoribonucleotide ligation facilitated by chemoselective acetylation

Nature Chemistry volume 5, pages 383389 (2013) | Download Citation

Abstract

The recent synthesis of pyrimidine ribonucleoside-2′,3′-cyclic phosphates under prebiotically plausible conditions has strengthened the case for the involvement of ribonucleic acid (RNA) at an early stage in the origin of life. However, a prebiotic conversion of these weakly activated monomers, and their purine counterparts, to the 3′,5′-linked RNA polymers of extant biochemistry has been lacking (previous attempts led only to short oligomers with mixed linkages). Here we show that the 2′-hydroxyl group of oligoribonucleotide-3′-phosphates can be chemoselectively acetylated in water under prebiotically credible conditions, which allows rapid and efficient template-directed ligation. The 2′-O-acetyl group at the ligation junction of the product RNA strand can be removed under conditions that leave the internucleotide bonds intact. Remarkably, acetylation of mixed oligomers that possess either 2′- or 3′-terminal phosphates is selective for the 2′-hydroxyl group of the latter. This newly discovered chemistry thus suggests a prebiotic route from ribonucleoside-2′,3′-cyclic phosphates to predominantly 3′,5′-linked RNA via partially 2′-O-acetylated RNA.

  • Compound C2H3NaOS

    Sodium thioacetate

  • Compound C3HN

    Cyanoacetylene

  • Compound C6D4N2S

    Tetradeuterio-β,β-dicyanovinylthioether

  • Compound C2N2

    Cyanogen

  • Compound C2H3N

    Methyl isonitrile

  • Compound C4H3N3

    N-Cyanoimidazole

  • Compound C5H6N2O

    N-Acetylimidazole

  • Compound C6FeK3N6

    Potassium ferricyanide

  • Compound C6FeK4N7

    Potassium ferrocyanide

  • Compound C4H6O2S2

    Diacetyl disulfide

  • Compound C9H12N3Na2O8P

    Disodium β-D-cytidine-3'-monophosphate

  • Compound C10H11N4Na2O8P

    Disodium β-D-inosine-3'-monophosphate

  • Compound C10H12N5Na2O8P

    Disodium β-D-guanosine-3'-monophosphate

  • Compound C9H11N2Na2O9P

    Disodium β-D-uridine-3'-monophosphate

  • Compound C10H12N5Na2O7P

    Disodium β-D-adenosine-3'-monophosphate

  • Compound C12H14N5Na2O8P

    Disodium 2'-O-acetyl-β-D-adenosine-3'-monophosphate

  • Compound C10H12N5Na2O7P

    Disodium β-D-adenosine-2'-monophosphate

  • Compound C10H11N5NaO6P

    Monosodium β-D-adenosine-2',3'-cyclic phosphate

  • Compound C12H14N5Na2O8P

    Disodium 3'-O-acetyl-β-D-adenosine-2'-monophosphate

  • Compound C30H34N15Na4O20P3

    Tetrasodium β-D-adenyl-(5'→3')-β-D-guanyl-(5'→3')-β-D-adenosine-3'-monophosphate

  • Compound C32H36N15Na4O21P3

    Tetrasodium β-D-adenyl-(5'→3')-β-D-guanyl-(5'→3')-2'-O-acetyl-β-D-adenosine-3'-monophosphate

  • Compound C30H33N15Na3O19P3

    Trisodium β-D-adenyl-(5'→3')-β-D-guanyl-(5'→3')-β-D-adenosine-2',3'-cyclic phosphate

  • Compound C30H34N15Na4O20P3

    Tetrasodium β-D-adenyl-(5'→3')-b-D-guanyl-(5'→3')-β-D-adenosine-2'-monophosphate

  • Compound C18H23N6Na3O15P2

    Trisodium β-D-cytidinyl-(5'→3')-β-D-cytidine-3'-monophosphate

  • Compound C18H23N6Na3O15P2

    Trisodium β-D-cytidinyl-(5'→3')-β-D-cytidine-2'-monophosphate

  • Compound C20H25N6Na3O16P2

    Trisodium β-D-cytidinyl-(5'→3')-2'-O-acetyl-β-D-cytidine-3'-monophosphate

  • Compound C20H25N6Na3O16P2

    Trisodium β-D-cytidinyl-(5'→3')-3'-O-acetyl-β-D-cytidine-2'-monophosphate

  • Compound C18H22N6Na2O14P2

    Disodium β-D-cytidinyl-(5'→3')-β-D-cytidine-2',3'-cyclic phosphate

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Acknowledgements

This work was funded by the Engineering and Physical Sciences Research Council through the provision of postdoctoral fellowships (C.D.D. and B.G.) and PhD studentships (M.W.P., S.I. and C.K.W.C.), the Medical Research Council through the provision of career development fellowships (F.R.B. and J.X., project no. MC_UP_A024_1009) and the Origin of Life Challenge, for which we thank H. Lonsdale. We thank C. Hilcenko, M. J. Churcher and V. B. Pinheiro for advice on polyacrylamide gel electrophoresis and fluorescence scanning, and D. Williams for advice on solid-phase oligonucleotide synthesis.

Author information

Author notes

    • Béatrice Gerland
    • , Saidul Islam
    •  & Matthew W. Powner

    Present addresses: Faculté de chimie, Université de Strasbourg, 1 rue Blaise Pascal, 67008 Strasbourg Cedex, France (B.G.); School of Biological and Chemical Sciences, Joseph Priestley Building, Queen Mary University London, Mile End Road, London E1 4NS, UK (S.I.); Department of Chemistry, University College London, Christopher Ingold Laboratories, 20 Gordon Street, London, WC1H 0AJ, UK (M.W.P.)

Affiliations

  1. Medical Research Council Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge Biomedical Campus, Cambridge CB2 0QH, UK

    • Frank R. Bowler
    • , Christopher K. W. Chan
    • , Colm D. Duffy
    • , John D. Sutherland
    •  & Jianfeng Xu
  2. School of Chemistry, The University of Manchester, Oxford Road, Manchester M13 9PL, UK

    • Béatrice Gerland
    • , Saidul Islam
    • , Matthew W. Powner
    •  & John D. Sutherland

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Contributions

F.R.B., C.K.W.C., C.D.D., B.G., S.I., M.W.P., J.D.S. and J.X. conceived and designed the experiments and analysed the data. F.R.B., C.K.W.C., C.D.D., B.G., S.I., M.W.P. and J.X. performed the experiments. F.R.B., S.I., M.W.P. and J.D.S. co-wrote the paper.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to John D. Sutherland.

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https://doi.org/10.1038/nchem.1626

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