Skip to main content
Log in

Selective amplification by auto- and cross-catalysis in a replicating peptide system

  • Letter
  • Published:

From Nature

View current issue Submit your manuscript

Abstract

Self-replication has been demonstrated in synthetic chemical systems based on oligonucleotides1,2,3,4,5,6,7, peptides8,9,10,11,12 and complementary molecules without natural analogues13,14,15,16. However, within a living cell virtually no molecule catalyses its own formation, and the search for chemical systems in which both auto- and cross-catalysis can occur has therefore attracted wide interest17. One such system, consisting of two self-replicating peptides that catalyse each other's production, has been reported10. Here we describe a four-component peptide system that is capable of auto- and cross-catalysis and allows for the selective amplification of one or more of the products by changing the reaction conditions. The ability of this system selectively to amplify one or more molecules in response to changes in environmental conditions such as pH or salt concentration supports the suggestion8 that self-replicating peptides may have played a role in the origin of life.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Figure 1: Percentage of each of the four products formed in the mixed fragment reactions (E1 + E2 + K1 + K2).
Figure 2: Schematic representation of all reaction pathways uncovered for the mixed fragment reaction E1 + E2 + K1 + K2 at pH 7.5.

Similar content being viewed by others

References

  1. von Kiedrowski, G. Aself-replicating hexadeoxynucleotide. Angew. Chem. Int. Edn Engl. 25, 932–935 (1986).

    Article  Google Scholar 

  2. von Kiedrowski, G., Wlotzka, B. & Helbing, J. Sequence dependence of template-directed syntheses of hexadeoxynucleotide derivatives with 3′-5′ pyrosphosphate linkage. Angew. Chem. Int. Edn Engl. 28, 1235–1237 (1989).

    Article  Google Scholar 

  3. von Kiedrowski, G., Wlotzka, B., Helbing, J., Matzen, M. & Jordan, S. Parabolic growth of a self-replicating hexadeoxynucleotide bearing a 3′-5′ phosphoamidate linkage. Angew. Chem. Int. Edn Engl. 30, 423–426 (1991).

    Article  Google Scholar 

  4. Sievers, D. & von Kiedrowski, G. Self-replication of complementary nucleotide-based oligomers. Nature 369, 221–224 (1994).

    Article  ADS  CAS  Google Scholar 

  5. Achilles, T. & von Kiedrowski, G. Aself-replicating system from three starting materials. Angew. Chem. Int. Edn Engl. 32, 1198–1201 (1993).

    Article  Google Scholar 

  6. Zielinski, W. S. & Orgel, L. E. Autocatalytic synthesis of a tetranucleotide analogue. Nature 327, 346–347 (1987).

    Article  ADS  CAS  Google Scholar 

  7. Li, T. & Nicolaou, K. C. Chemical self-replication of palindromic duplex DNA. Nature 369, 218–221 (1994).

    Article  ADS  CAS  Google Scholar 

  8. Lee, D. H., Granja, J. R., Martinez, J. A., Severin, K. & Ghadiri, M. R. Aself-replicating peptide. Nature 382, 525–528 (1996).

    Article  ADS  CAS  Google Scholar 

  9. Severin, K., Lee, D. H., Kennan, A. J. & Ghadiri, M. R. Asynthetic peptide ligase. Nature 389, 706–709 (1997).

    Article  ADS  CAS  Google Scholar 

  10. Lee, D. H., Granja, J. A., Severin, K., Yokobayashi, Y. & Ghadiri, M. R. Emergence of symbiosis in peptide self-replication through a hypercyclic network. Nature 390, 591–594 (1997).

    Article  ADS  CAS  Google Scholar 

  11. Yao, S., Ghosh, I., Zutshi, R. & Chmielewski, J. ApH-modulated, self-replicating peptide. J. Am. Chem. Soc. 119, 10559–10560 (1997).

    Article  CAS  Google Scholar 

  12. Yao, S., Ghosh, I., Zutshi, R. & Chmielewski, J. Aself-replicating peptide under ionic control. Angew. Chem. Int. Edn Engl. 37, 478–481 (1998).

    Article  CAS  Google Scholar 

  13. Tjivikua, T., Ballester, P. & Rebek, J. J Aself-replicating system. J. Am. Chem. Soc. 112, 1249–1250 (1990).

    Article  CAS  Google Scholar 

  14. Nowick, J. S., Feng, Q., Tjivikua, T., Ballester, P. & Rebek, J. J Kinetic studies and modeling of a self-replicating system. J. Am. Chem. Soc. 113, 8831–8839 (1991).

    Article  CAS  Google Scholar 

  15. Wintner, E. A., Conn, M. M. & Rebek, J. J Self-replicating molecules: a second generation. J. Am. Chem. Soc. 116, 8877–8884 (1994).

    Article  CAS  Google Scholar 

  16. Wintner, E. A., Tsao, B. & Rebek, J. J Evidence against an alternative mechanism for a self-replicating system. J. Org. Chem. 60, 7997–8001 (1995).

    Article  CAS  Google Scholar 

  17. Orgel, L. E. Unnatural selection in chemical systems. Acc. Chem. Res. 28, 109–118 (1995).

    Article  CAS  Google Scholar 

  18. Zhou, N. E., Kay, C. M. & Hodges, R. S. The role of interhelical ionic interactions in controlling protein folding and stability. De novo designed synthetic two-stranded alpha-helical coiled-coils. J. Mol. Biol. 237, 500–512 (1994).

    Article  CAS  Google Scholar 

  19. Dawson, P. E., Muir, T. W., Clark-Lewis, I. & Kent, S. B. Synthesis of proteins by native chemical ligation. Science 266, 776–779 (1994).

    Article  ADS  CAS  Google Scholar 

  20. Kramer, F. R., Mills, D. R., Cole, P. E., Nishihana, T. & Spiegelman, S. Evolution in vitro: sequence and phenotype of a mutant RNA resistant to ethidium bromide. J. Mol. Biol. 89, 719–736 (1974).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This work was supported by the NSF.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Jean Chmielewski.

Supplementary Information

Rights and permissions

Reprints and permissions

About this article

Cite this article

Yao, S., Ghosh, I., Zutshi, R. et al. Selective amplification by auto- and cross-catalysis in a replicating peptide system. Nature 396, 447–450 (1998). https://doi.org/10.1038/24814

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/24814

  • Springer Nature Limited

This article is cited by

Navigation