1 Section II. Building 18.2, Department of Cellular and Molecular Medicine, Faculty of Health and Medical Sciences, Københavns Universitet2 RNA and Gene Medicine Program, Department of Cellular and Molecular Medicine, Faculty of Health and Medical Sciences, Københavns Universitet3 Section II. Building 18.2, Department of Cellular and Molecular Medicine, Faculty of Health and Medical Sciences, Københavns Universitet
We report the first PNA self-replicating system based on template directed cross-catalytic ligation, a process analogous to biological replication. Using two template PNAs and four pentameric precursor PNAs, all four possible carbodiimide assisted amide ligation products were detected and identified by HPLC and MALDI-TOF analysis. We conclude that the two template complementary reaction products are generated via cross-catalysis, while the other two self-complementary (and in principle auto-catalytic) products are formed via intra-complex coupling between the two sets of complementary PNA precursors. Cross-catalytic product formation followed product inhibited kinetics, but approximately two replication rounds were observed. Analogous but less efficient replication was found for a similar tetrameric system. These results demonstrate that simpler nucleobase replication systems than natural oligonucleotides are feasible, thereby strengthening the foundation for the discussion of a possible role for PNA (like) genetic material in the prebiotic evolution of life and lay the ground for further studies into evolution of such potentially prebiotic systems.
Organic and Biomolecular Chemistry, 2014, Vol 12, Issue 35, p. 6901-6907