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Self-replication of complementary nucleotide-based oligomers


THE development of non-enzymatic self-replicating systems based on autocatalytic template-directed reactions is a current objective of bioorganic chemistry1–6. Typically, a self-complementary template molecule AB is synthesized autocatalytically from two complementary template fragments A and B7–16. Natural replication of nucleic acids, however, utilizes complementary rather than self-complementary strands. Here we report on a minimal implementation of this type of replication17 based on cross-catalytic template-directed syntheses of hexadeoxy nucleotide derivatives from amino-trideoxynucleotides. In our experiments, two self-complementary and two complementary templates compete for their combinatorial synthesis from four common trimeric precursors. We provide kinetic evidence that cross-catalytic self-replication of complementary templates can proceed with an efficiency similar to that of autocatalytic self-replication of self-complementary templates. We observe selective stimulation of template synthesis, and thus information transfer, on seeding the reaction mixtures with one of four chemically labelled templates bearing the sequence of the reaction products. Our results bring a stage closer the development of schemes that might explain how replicating systems based on nucleic acids arose on the prebiotic Earth.

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  1. 1

    Orgel, L. E. Nature 358, 203–209 (1992).

    ADS  CAS  Article  Google Scholar 

  2. 2

    Hoffman, S. Angew. Chem. int. Edn engl. 31, 1013–1016 (1992).

    Article  Google Scholar 

  3. 3

    Eschenmoser, A. & Loewenthal, E. Chem. Soc. Rev. 21, 1–16 (1992).

    CAS  Article  Google Scholar 

  4. 4

    Bachmann, P. A., Luisi, P. L. & Lang, J. Nature 357, 57–59 (1992).

    ADS  CAS  Article  Google Scholar 

  5. 5

    Famulok, J. S., Nowick, J. & Rebek, J. Acta. chem. scand. 46, 315–324 (1992).

    CAS  Article  Google Scholar 

  6. 6

    von Kiedrowski, G. Bioorg. Chem. Front. 3, 113–146 (1993).

    CAS  Article  Google Scholar 

  7. 7

    von Kiedrowski, G. Angew. Chem. Int. Edn engl. 25, 932–935 (1986).

    Article  Google Scholar 

  8. 8

    Zielinski, W. S. & Orgel, L. E. Nature 327, 346–347 (1987).

    ADS  CAS  Article  Google Scholar 

  9. 9

    von Kiedrowski, G., Wlotzka, B. & Helbing, J. Angew. Chem. int. Edn engl. 28, 1235–1237 (1989).

    Article  Google Scholar 

  10. 10

    Tjivikua, T., Ballester, P. & Rebek, J. J. Am. chem. Soc. 112, 1249–1250 (1990).

    CAS  Article  Google Scholar 

  11. 11

    von Kiedrowski, G., Wlotzka, B., Helbing, J., Matzen, M. & Jordan, S. Angew. Chem. int. Edn. engl. 30, 423–426 and 892 (1991).

    Article  Google Scholar 

  12. 12

    Terfort, A. & von Kiedrowski, G. Angew. Chem. int. Edn engl. 31, 654–656 (1992).

    Article  Google Scholar 

  13. 13

    Hong, J.-I., Feng, Q., Rotello, V. & Rebek, J. Science 255, 848–850 (1992).

    ADS  CAS  Article  Google Scholar 

  14. 14

    Feng, Q., Park, T. K. & Rebek, J. Science 256, 1179–1180 (1992).

    ADS  CAS  Article  Google Scholar 

  15. 15

    Böhler, C., Bannwarth, W. Luisi, P. L. Helv. chim. Acta 76, 2313–2320 (1993).

    Article  Google Scholar 

  16. 16

    Achilles, T. & von Kiedrowski, G. Angew. Chem. int. Edn engl. 32, 1198–1201 (1993).

    Article  Google Scholar 

  17. 17

    Kanavarioti, A. J. Theor. Biol. 158, 207–219 (1992).

    CAS  Article  Google Scholar 

  18. 18

    Wlotzka, B. thesis, Univ. Göttingen (1992).

  19. 19

    Dolinnaya, N. G., Tsytovich, A. V., Sergeev, V. N., Oretskaya, T. S. & Shabarova, Z. A. Nucleic Acids Res. 19, 3073–3080 (1991).

    CAS  Article  Google Scholar 

  20. 20

    Inoue, T. & Orgel, L. E. Science 219, 859–862 (1983).

    ADS  CAS  Article  Google Scholar 

  21. 21

    Szathmáry, E. Trends Ecol. Evol. 6, 366–370 (1991).

    Article  Google Scholar 

  22. 22

    Eigen, M. & Schuster, P. The Hypercycle. A Principle of Natural Self-Organization (Springer, Berlin, 1979).

    Google Scholar 

  23. 23

    Kauffman, S. A. The Origins of Order (Oxford Univ. Press, New York, 1993).

    Google Scholar 

  24. 24

    Ferris, J. P. & Ertem, G. J. Am. chem. Soc. 115, 12270–12275 (1993).

    CAS  Article  Google Scholar 

  25. 25

    Li, T. & Nicolaou, K. C. Nature 369, 218–221 (1994).

    ADS  CAS  Article  Google Scholar 

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

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