Elongation of Model Prebiotic Proto-Peptides by Continuous Monomer Feeding

Mixtures of amino acids with hydroxy acids allow for the formation of peptide bonds in a plausible prebiotic scenario via ester bond formation followed by ester–amide exchange. Here, we investigate the ability of the ester-mediated reaction pathway to form even longer polymers with peptide backbones based on the specific details of the reaction protocol. Fresh monomers were fed to the polymer/monomer mixture periodically by an automated “day–night machine” that was designed to simulate wet–dry cycles that would have been common on the prebiotic Earth. Quantitative analysis of peptide bond formation in the complex oligomer mixture was enabled by a simple hydrolysis treatment. In the ester-mediated peptide elongation process, new monomers add to one end of the chain step-by-step without termination. The feed composition (hydroxy acids and/or amino acids) was found to determine the final oligomer distribution. Production of longer oligomers enriched in peptide bonds was more efficient when only amino acids were fed because of a smaller number of active oligomer chains. These results reveal a process for synthesizing longer depsipeptides and/or peptides that could form secondary structures, and possibly functional polymers.