Thioesters provide a plausible prebiotic path to proto-peptides.

It is widely assumed that the condensation of building blocks into oligomers and polymers was important in the origins of life. High activation energies, unfavorable thermodynamics and side reactions are bottlenecks for abiotic peptide formation. All abiotic reactions reported thus far for peptide bond formation via thioester intermediates have relied on high energy molecules, which usually suffer from short half-life in aqueous conditions and therefore require constant replenishment. Here we report plausible prebiotic reactions of mercaptoacids with amino acids that result in the formation of thiodepsipeptides, which contain both peptide and thioester bonds. Thiodepsipeptide formation was achieved under a wide range of pH and temperature by simply drying and heating mercaptoacids with amino acids. Our results offer a robust one-pot prebiotically-plausible pathway for proto-peptide formation. These results support the hypothesis that thiodepsipeptides and thiol-terminated peptides formed readily on prebiotic Earth and were possible contributors to early chemical evolution.