Cross-catalytic peptide nucleic acid (PNA) replication based on templated ligation

Org Biomol Chem. 2014 Sep 21;12(35):6901-7. doi: 10.1039/c4ob01158a.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biochemistry / methods*
  • Carbodiimides / chemistry
  • Catalysis
  • Chromatography, High Pressure Liquid
  • DNA Replication
  • Hydrogen-Ion Concentration
  • Kinetics
  • Nucleic Acid Conformation
  • Oligonucleotides
  • Peptide Nucleic Acids / chemistry*
  • Protein Structure, Tertiary
  • Solvents / chemistry
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
  • Temperature
  • Templates, Genetic

Substances

  • Carbodiimides
  • Oligonucleotides
  • Peptide Nucleic Acids
  • Solvents