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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.

References

  1. Powner, M. W., Gerland, B. & Sutherland, J. D. Synthesis of activated pyrimidine ribonucleotides in prebiotically plausible conditions. Nature 459, 239–242 (2009).

    Article  CAS  PubMed  Google Scholar 

  2. Powner, M. W., Sutherland, J. D. & Szostak, J. W. Chemoselective multicomponent one-pot assembly of purine precursors in water. J. Am. Chem. Soc. 132, 16677–16688 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Springsteen, G. & Joyce, G. F. Selective derivatization and sequestration of ribose from a prebiotic mix. J. Am. Chem. Soc. 126, 9578–9583 (2004).

    Article  CAS  PubMed  Google Scholar 

  4. Borsenberg, V. et al. Exploratory studies to investigate a linked prebiotic origin of RNA and coded peptides. Chem. Biodivers. 1, 203–246 (2004).

    Article  Google Scholar 

  5. Joyce, G. F. et al. Chiral selection in poly(C)-directed synthesis of oligo(G). Nature 310, 602–604 (1984).

    Article  CAS  PubMed  Google Scholar 

  6. Wade, N. Chemist shows how RNA can be starting point for life. The New York Times 14 May 2009.

  7. Woese, C. The Genetic Code (Harper & Row, 1968).

    Google Scholar 

  8. Budin, I. & Szostak, J. W. Expanding roles for diverse physical phenomena during the origin of life. Annu. Rev. Biophys. 39, 245–263 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Blackmond, D. in The Origins of Life (eds Deamer, D. & Szostak, J. W.) 123–139 (Cold Spring Harbor Laboratory Press, 2010).

    Google Scholar 

  10. Miller, S. L. Production of amino acids under possible primitive earth conditions. Science 117, 528–529 (1953).

    Article  CAS  PubMed  Google Scholar 

  11. Shock, E. L. & Shulte, M. D. Summary and implications of reported amino acid concentrations in the murchison meteorite. Geochim. Cosmochim. Acta 54, 3159–3173 (1990).

    Article  CAS  PubMed  Google Scholar 

  12. Glavin, D. P. & Dworkin, J. P. Enrichment of the amino acid L-isovaline by aqueous alteration on Cl and CM meteorite parent bodies. Proc. Natl Acad. Sci. USA 106, 5487–5492 (2009).

    Article  CAS  PubMed  Google Scholar 

  13. Pizzarello, S. The chemistry of life's origin: a carbonaceous meteorite perspective. Acc. Chem. Res. 39, 231–237 (2006).

    Article  CAS  PubMed  Google Scholar 

  14. Klussmann, M. et al. Thermodynamic control of asymmetric amplification in amino acid catalysis. Nature 441, 621–623 (2006).

    Article  CAS  PubMed  Google Scholar 

  15. Klussmann, M., White, A. J. P., Armstrong, A. & Blackmond, D. G. Rationalization and prediction of solution enantiomeric excess in ternary phase systems. Angew. Chem. Int. Ed. 47, 7985–7989 (2006).

    Article  Google Scholar 

  16. Klussmann, M., Izumi, T., White, A. J. P., Armstrong, A. & Blackmond, D. G. Emergence of solution-phase homochirality via crystal engineering of amino acids. J. Am. Chem. Soc. 123, 7657–7660 (2007).

    Article  Google Scholar 

  17. Viedma, C., Ortiz, T., de Torres, J. E., Izumi, T. & Blackmond, D. G. Evolution of solid phase homochirality for a proteinogenic amino acid. J. Am. Chem. Soc. 130, 15274–15275 (2008).

    Article  CAS  PubMed  Google Scholar 

  18. Morowitz, H. A mechanism for the amplification of fluctuations in racemic mixtures. J. Theor. Biol. 25, 491–494 (1969).

    Article  CAS  PubMed  Google Scholar 

  19. Breslow, R. & Levine, M. Amplification of enantiomeric concentrations under credible prebiotic conditions. Proc. Natl Acad. Sci. USA 103, 12979–12980 (2006).

    Article  CAS  PubMed  Google Scholar 

  20. Hayashi, Y. et al. Large nonlinear effect observed in the enantiomeric excess of proline in solution and that in the solid state. Angew. Chem. Int. Ed. 45, 4593–4597 (2006).

    Article  CAS  Google Scholar 

  21. Breslow, R. & Cheng, Z. L. L-Amino acids catalyze the formation of an excess of D-glyceraldehyde, and thus of other D sugars, under credible prebiotic conditions. Proc. Natl Acad. Sci. USA 107, 5723–5725 (2010).

    Article  CAS  PubMed  Google Scholar 

  22. Breslow, R. & Cheng, Z. L. On the origin of terrestrial homochirality for nucleosides and amino acids. Proc. Natl Acad. Sci. USA 106, 9144–9146 (2009).

    Article  CAS  PubMed  Google Scholar 

  23. Viedma, C. Chiral symmetry breaking during crystallization: complete chiral purity induced by nonlinear autocatalysis and recycling. Phys. Rev. Lett. 94, 065504 (2005).

    Article  PubMed  Google Scholar 

  24. Ashwell, M., Tandon, M. & Lapierre, J. P. Synthesis of imidazooxazole and imidazothiazole inhibitors of P38 MAP kinase. World patent WO-2006044869 (2006).

  25. Bonner, W. A. Origins of chiral homogeneity in nature. Top. Stereochem. 18, 1–96 (1988).

    CAS  Google Scholar 

  26. Balavoine, G., Moradpour, A. & Kagan, H. B. Preparation of chiral compounds with high optical purity by irradiation with circularly polarized light, a model reaction for the prebiotic generation of optical activity. J. Am. Chem. Soc. 96, 5152–5158 (1974).

    Article  CAS  Google Scholar 

  27. Flores, J. J., Bonner, W. A. & Massey, G. A. Asymmetric photolysis of (rs)-leucine with circularly polarized ultraviolet light. J. Am. Chem. Soc. 99, 3622–3625 (1977).

    Article  CAS  PubMed  Google Scholar 

  28. Anastasi, C., Crowe, M. A., Powner, M. W. & Sutherland, J. D. Direct assembly of nucleoside precursors from two- and three-carbon units. Angew. Chem. Int. Ed. 45, 6176–6179 (2006).

    Article  CAS  Google Scholar 

  29. Powner, M. W. & Sutherland, J. D. Phosphate-mediated interconversion of ribo- and arabino-configured prebiotic nucleotide intermediate. Angew. Chem. Int. Ed. 49, 4641–4643 (2010).

    Article  CAS  Google Scholar 

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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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