Chemical Primer Extension

The copying of genetic information usually occurs via enzymatically catalyzed elongation of a short oligonucleotide, dubbed 'primer' that binds to the template. The enzymes that catalyze primer extension are called 'polymerases', and their substrates are usually nucleoside triphosphates (NTPs or dNTPs). The best-known application that utilizes enzymatically catalyzed primer extension is the polymerase chain reaction (PCR), which was invented by Mullis. It is less well known that primer extension can also be induced in the absence of enzymes, solely based on molecular recognition of activated nucleotides and the template-primer duplex. This version of the reaction is called enzyme-free or 'chemical primer reaction'. It is relevant for the origin of life and can be used for SNP genotyping.

References

PCR

[1] K. B. Mullis, The polymerase chain reaction (Nobel Lecture). Angew. Chem. Int. Ed. Engl. 1994, 33, 1209-1213. https://doi.org/10.1002/anie.199412091

Chemical Primer Extension

[2] M. Zielinski, I. A. Kozlov, L. E. Orgel, A comparison of RNA with DNA in template-directed synthesis. Helv. Chim. Acta 2000, 83, 1678-1684. https://doi.org/10.1002/1522-2675(20000809)83:8%3C1678::AID-HLCA1678%3E3.0.CO;2-P

[3] J. A. Rojas Stütz, E. Kervio, C. Deck, C. Richert, Chemical primer extension - individual steps of spontaneous replication. Chem. Biodiv. 2007, 4, 784-802. https://doi.org/10.1002/cbdv.200790064

[4] N. Griesang, K. Giessler, T. Lommel, C. Richert, Four color, enzyme-free interrogation of DNA sequences with chemically activated, 3'-fluorophore-labeled nucleotides. Angew. Chem. Int. Ed. 2006, 45 , 6144-6148. https://doi.org/10.1002/anie.200600804