Nature 382, 525 - 528 (08 August 1996); doi:10.1038/382525a0

A self-replicating peptide

David H. Lee, Juan R. Granja, Jose A. Martinez, Kay Severin & M. Reza Ghadiri

Departments of Chemistry and Molecular Biology and the Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, California 92037, USA

THE production of amino acids and their condensation to polypeptides under plausibly prebiotic conditions have long been known^1,2. But despite the central importance of molecular self-replication in the origin of life, the feasibility of peptide self-replication has not been established experimentally³⁻⁶. Here we report an example of a self-replicating peptide. We show that a 32-residue -helical peptide based on the leucine-zipper domain of the yeast transcription factor GCN4 can act autocatalytically in templating its own synthesis by accelerating the thioester-promoted amide-bond condensation of 15- and 17-residue fragments in neutral, dilute aqueous solutions. The self-replication process displays parabolic growth pattern with the initial rates of product formation correlating with the square-root of initial template concentration.

References

1.	Miller, S. L. & Orgel, L. E. The Origins of Life on the Earth (Prentice Hall, Englewood Cliffs, NJ, 1974).
2.	Fox, S. W. & Dose, K. Molecular Evolution and the Origin of Life (Dekker, New York, 1977).
3.	Orgel, L. E. Nature 358, 203−209 (1992). | Article | PubMed | ChemPort |
4.	Oparin, A. I. Adv. Enzymol. 27, 347−380 (1965). | PubMed | ChemPort |
5.	Dyson, F. J. J. Molec. Evol. 18, 344−350 (1982). | PubMed | ChemPort |
6.	Kauffman, S. A. J. theor. Biol. 119, 1−24 (1986). | PubMed | ISI | ChemPort |
7.	von Kiedrowski, G. Angew. Chem. int. Edn. engl. 25, 932−935 (1986). | Article |
8.	Zielinski, W. S. & Orgel, L. E. Nature 327, 346−347 (1987). | Article | PubMed | ISI | ChemPort |
9.	von Kiedrowski, G., Wlotzka, B. & Helbing, J. Angew. Chem. int. Edn. engl. 28, 1235−1237 (1989). | Article |
10.	Tjivikua, T., Ballester, P. & Rebek, J. Jr J. Am. chem. Soc. 112, 1249−1250 (1990). | Article | ISI | ChemPort |
11.	Nowick, J. S., Feng, Q., Tjivikua, T., Ballester, P. & Rebek, J. Jr J. Am. chem. Soc. 113, 8831−8839 (1991). | Article | ISI | ChemPort |
12.	von Kiedrowski, G., Wlotzka, B., Helbing, J., Matzen, M. & Jordan, S. Angew Chem. int. Edn. engl. 30, 423−426 (1991). | Article |
13.	Winter, E. A., Conn, M. M. & Rebek, J. Jr J. Am. chem. Soc. 116, 8877−8884 (1994). | ISI | ChemPort |
14.	Li, T. & Nicolaou, K. C. Nature 369, 218−221 (1994). | Article | PubMed | ISI | ChemPort |
15.	Pitsch, S. et al. Helv. chim. Acta 78, 1621−1635 (1995). | Article | ISI | ChemPort |
16.	Sievers, D. & von Kiedrowski, G. Nature 369, 221−224 (1994). | Article | PubMed | ISI | ChemPort |
17.	Harbury, P. B., Zhang, T., Kim, P. S. & Alber, T. Science 262, 1401−1407 (1993). | PubMed | ISI | ChemPort |
18.	Zhou, N. E., Kay, C. M. & Hodges, R. S. Biochemistry 31, 5739−5746 (1992). | Article | PubMed | ISI | ChemPort |
19.	Dawson, P. E., Muir, T. W., Clark-Lewsi, I. & Kent, S. B. H. Science 266, 776−779 (1994). | PubMed | ISI | ChemPort |
20.	von Kiedrowski, G. Bioorg. Chem. Front. 3, 113−146 (1993). | ChemPort |
21.	Wintner, E. A., Tsao, B. & Rebek, J. Jr J. org. Chem. 60, 7997−8001 (1995). | Article | ISI | ChemPort |
22.	Hu, J. C., O'Shea, E. K., Kim, P. S. & Sauer, R. T. Science 250, 1400−1403 (1990). | PubMed | ISI | ChemPort |
23.	Ghadiri, M. R., Granja, J. R., Milligan, R. A., McRee, D. E. & Khazanovich, N. Nature 366, 324−327 (1993). | Article | PubMed | ISI | ChemPort |
24.	Kobayashi, K., Granja, J. R. & Ghadiri, M. R. Angew. Chem. int. Edn. engl. 34, 95−98 (1995). | ChemPort |
25.	Bennett, M. J., Schlungger, M. P. & Eisenberg, D. Proat. Sci. 4, 2455−2468 (1995). | ChemPort |