A Self-Replicating Peptide Nucleic Acid

TL;DR

This study demonstrates autocatalytic, template-directed synthesis of a self-complementary peptide nucleic acid (PNA), revealing factors influencing reaction kinetics and optimizing conditions for enhanced autocatalytic efficiency.

Contribution

It presents the first detailed kinetic analysis and optimization of self-replicating PNA systems, highlighting factors that significantly improve autocatalytic efficiency.

Findings

Kinetic modeling shows parabolic growth following the square-root law.

Reaction rate and template effect are influenced by catalysts, pH, and co-solvents.

Reaction conditions optimized increased autocatalytic efficiency by two orders of magnitude.

Abstract

We report on a case of 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 product by means of RP-HPLC. Kinetic modeling with the SimFit program revealed parabolic growth according to the so-called square-root law. The observed template effect, as well as the rate of the ligation, was significantly influenced by factors like 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.