A plausible pathway to prebiotic peptides via amino acid amides on the primordial Earth

The prebiotic synthesis of peptides prior to ribosome-catalyzed processes remains an enigma. The synthesis of abiotic peptides from amino acids (AAs) is primarily constrained by high activation energies and unfavorable thermodynamics, necessitating the identification of plausible prebiotic alternatives for synthesizing prebiotic peptides. Here we present a plausible pathway to the formation of prebiotic peptides, wherein oligopeptides, oligopeptide amides, and cyclic oligopeptides can be directly synthesized from amino acid amides (AA-NH₂) under wet–dry cycle conditions without the need for any enhancers. The subsequent investigation revealed that AA-NH₂ demonstrated more favorable thermodynamic reaction effects than AAs in peptide formation. In contrast to the polymerization of AAs, the process of peptide formation through the polymerization of AA-NH₂ was significantly simplified. Additionally, AA-NH₂ was discovered to function as a “bridge” for the formation of peptides from AAs, thereby facilitating their participation in the synthesis of intricate peptide structures. On the basis of these findings, a plausible mechanism for the prebiotic origin network of peptides under primordial Earth conditions has been proposed. Overall, this research presents a plausible pathway for the generation of prebiotic peptides and peptide libraries within prebiotic environments.