Surface-promoted replication and exponential amplification of DNA analogues

A. Luther, R. Brandsch and G. von Kiedrowski ()
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A. Luther: Lehrstuhl für Bioorganische Chemie, Ruhr-Universität Bochum
R. Brandsch: Lehrstuhl für Bioorganische Chemie, Ruhr-Universität Bochum
G. von Kiedrowski: Lehrstuhl für Bioorganische Chemie, Ruhr-Universität Bochum

Nature, 1998, vol. 396, issue 6708, 245-248

Abstract: 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.

Date: 1998
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DOI: 10.1038/24343

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