A self-replicating peptide nucleic acid.

While the non-enzymatic ligation and template-directed synthesis of peptide nucleic acids (PNA) have been reported since 1995, a case of self-replication of PNA has not been achieved yet. Here, we present evidence for autocatalytic feedback in a template directed synthesis of a self-complementary hexa-PNA from two trimeric building blocks. The course of the reaction was monitored in the presence of increasing initial concentrations of the product by RP-HPLC. Kinetic modeling with the SimFit program revealed parabolic growth characteristics. The observed template effect, as well as the rate of ligation, was significantly influenced by nucleophilic catalysts, pH value, and uncharged co-solvents. Systematic optimization of the reaction conditions allowed us to increase the autocatalytic efficiency of the system by two orders of magnitude. Our findings contribute to the hypothesis that PNA may have served as a primordial genetic molecule and was involved in a potential precursor of a RNA world.