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A route to enantiopure RNA precursors from nearly racemic starting materials

Nature Chemistry volume 3, pages 704–706 (2011)Cite this article

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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.

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Figure 1: Racemic glyceraldehyde is converted into enantioenriched RNA precursors in the presence of a chiral amino acid.
Figure 2: Route to enantiopure RNA precursors from racemic glyceraldehyde and slightly enantioenriched amino 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, 92037, California, USA

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

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  1. Jason E. Hein
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  2. Eric Tse
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  3. 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.

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Correspondence to Donna G. Blackmond.

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The authors declare no competing financial interests.

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Hein, J., Tse, E. & Blackmond, D. A route to enantiopure RNA precursors from nearly racemic starting materials. Nature Chem 3, 704–706 (2011). https://doi.org/10.1038/nchem.1108

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