Article | Published:

A route to enantiopure RNA precursors from nearly racemic starting materials

Nature Chemistry volume 3, pages 704706 (2011) | Download Citation

Abstract

The single-handedness of biological molecules is critical for molecular recognition and replication processes and would seem to be a prerequisite for the origin of life. A drawback of recently reported synthetic routes to RNA is the requirement for enantioenriched reactants, which fails to address the puzzle of how the single chirality of biological molecules arose. Here, we report the synthesis of highly enantioenriched RNA precursor molecules from racemic starting materials, with the molecular asymmetry derived solely from a small initial imbalance of the amino-acid enantiomers present in the reaction mixture. Acting as spectators to the main reaction chemistry, the amino acids orchestrate a sequence of physical and chemical amplification processes. The emergence of molecules of single chirality from complex, multi-component mixtures supports the robustness of this synthesis process under potential prebiotic conditions and provides a plausible explanation for the single-handedness of biological molecules before the emergence of self-replicating informational polymers.

  • Compound C3H6O3

    D-Glyceraldehyde

  • Compound C3H6O3

    L-Glyceraldehyde

  • Compound C3H4N2O

    Oxazol-2-amineoxazol-2-amine

  • Compound C3H7NO2

    L-Alanine

  • Compound C6H14N4O2

    L-Arginine

  • Compound C4H8N2O3

    L-Asparagine

  • Compound C4H7NO4

    L-Aspartic acid

  • Compound C3H7NO2S

    L-Cysteine

  • Compound C5H10N2O3

    L-Glutamine

  • Compound C5H9NO4

    L-Glutamic adid

  • Compound C2H5NO2

    Glycine

  • Compound C6H9N3O2

    L-Histidine

  • Compound C6H13NO2

    L-Isoleucine

  • Compound C6H13NO2

    L-Leucine

  • Compound C5H12N2O2

    L-Lysine

  • Compound C5H11NO2S

    L-Methionine

  • Compound C9H11NO2

    L-Phenylalanine

  • Compound C5H9NO2

    L-Proline

  • Compound C3H7NO3

    L-Serine

  • Compound C4H9NO3

    L-Threonine

  • Compound C11H12N2O2

    L-Trytophan

  • Compound C9H11NO3

    L-Tyrosine

  • Compound C5H11NO2

    L-Valine

  • Compound C6H10N2O4

    (3aS,5R,6R,6aR)-2-Amino-5-(hydroxymethyl)-3a,5,6,6a-tetrahydrofuro[2,3-d]oxazol-6-ol(3aS,5R,6R,6aR)-2-amino-5-(hydroxymethyl)-3a,5,6,6a-tetrahydrofuro[2,3-d]oxazol-6-ol

  • Compound C6H10N2O4

    (3aR,5R,6R,6aS)-2-Amino-5-(hydroxymethyl)-3a,5,6,6a-tetrahydrofuro[2,3-d]oxazol-6-ol

  • Compound C11H17N3O5

    (2S)-1-((5S)-2-Amino-5-(hydroxymethyl)-3a,5,6,6a-tetrahydrofuro[2,3-d]oxazol-6-yl)pyrrolidine-2-carboxylic acid

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Acknowledgements

The authors thank A. Rheingold and C. Moore (UCSD) for performing X-ray crystallography, W. Uritboonthai and G. Suizdak (TSRI Center for Mass Spectrometry) for carrying out high-resolution mass spectrometry, and L. Pasternak and D.-H. Huang (TSRI NMR facility) for assistance with NMR spectroscopy and analysis. The authors also thank G.F. Joyce (TSRI) for scientific discussions and for critical reading of the manuscript.

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  1. Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA

    • Jason E. Hein
    • , Eric Tse
    •  & Donna G. Blackmond

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Contributions

D.G.B. conceived this work and wrote the paper. J.E.H. designed and carried out the experiments. E.T. carried out preliminary work.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Donna G. Blackmond.

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DOI

https://doi.org/10.1038/nchem.1108

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