Surface-promoted replication and exponential amplification of DNA analogues (original) (raw)

Nature volume 396, pages 245–248 (1998)Cite this article

Abstract

Self-replicating chemical systems have been designed and studied to identify the minimal requirements for molecular replication1, to translate the principle into synthetic supramolecular systems2 and to derive a better understanding of the scope and limitations of self-organization processes3 that are believed to be relevant to the origin of life on Earth4. Current implementations make useofoligonucleotide analogues5,6,7,8,9,10,11,12, peptides13,14,15,16,17, and other molecules18,19,20,21,22,23,24 as templates and are based either on autocatalytic, cross-catalytic, or collectively catalytic pathways for template formation. A common problem of these systems is product inhibion, leading to parabolic instead of exponential amplification25. The latter is the dynamic prerequisite for selection in the darwinian sense26,27. We here describe an iterative, stepwise procedure for chemical replication which permits an exponential increase in the concentration of oligonucleotide analogues. The procedure employs the surface of a solid support and is called SPREAD (surface-promoted replication and exponential amplification of DNA analogues). Copies are synthesized from precursor fragments by chemical ligation on immobilized templates, and then liberated and immobilized to become new templates. The process is repeated iteratively. The role of the support is to separate complementary templates which would form stable duplexes in solution. SPREAD combines the advantages of solid-phase chemistry with chemical replication, and can be further developed for the non-enzymatic and enzymatic amplification of RNA, peptides and other templates as well as for studies of in vitro evolution and competition in artificial chemical systems. Similar processes may also have played a role in the origin of life on Earth, because the earliest replication systems may have proliferated by spreading on mineral surfaces28,29,30,31,32,33.

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Figure 1: General scheme of the SPREAD procedure.

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Figure 2: Oligonucleotide analogues and reactions employed in the experiment.

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Figure 3: HPLC analysis of products under denaturing conditions obtained in the consecutive steps of a SPREAD cycle.

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Figure 4: Pathway of template transfers in the course of three cycles of SPREAD amplification.

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Acknowledgements

This work was supported by Deutsche Forschungsgemeinschaft (SFB 452), Fonds der Chemischen Industrie, German Israeli Foundation (GIF) and Bundesministerium für Bildung und Forschung (BMBF). We thank B. Materne and M. Wüstefeld for technical assistance, B. Kind for mathematical advice, and K. Johnsson and M. Zielinski for comments and suggestions on the manuscript.

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  1. Lehrstuhl für Bioorganische Chemie, Ruhr-Universität Bochum, Universitätstrasse 150, NC 2/173, D-44780, Bochum, Germany
    A. Luther, R. Brandsch & G. von Kiedrowski

Authors

  1. A. Luther
  2. R. Brandsch
  3. G. von Kiedrowski

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Correspondence toG. von Kiedrowski.

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Luther, A., Brandsch, R. & von Kiedrowski, G. Surface-promoted replication and exponential amplification of DNA analogues.Nature 396, 245–248 (1998). https://doi.org/10.1038/24343

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