Protopeptide backbone affects assembly in aqueous solutions

One of the most fascinating mysteries in the field of origins of life concerns the driving force that led to the selection of today’s 20 universal _L-alpha amino acids in biology. An essential aspect of life’s emergence involves the formation of compartments, which offer encapsulation for target molecules and provide protection from hydrolysis in aqueous environments. Thus, polymers capable of assembly may have had a chemical evolutionary advantage over polymers that lacked this ability. We postulated that primordial peptide assembly could be one of the driving forces that led to the chemical selection of alpha amino acids in life today. To test this hypothesis, we generated depsipeptides, oligomers composed of ester bonds and peptide bonds that form readily under mild drying conditions, as model prebiotic peptides. However, it is unknown whether depsipeptides form assemblies in an aqueous environment similarly to peptides and proteins. To test the hypothesis that depsipeptides with alpha backbones will form assemblies more readily than beta backbones, we synthesized depsipeptides using a matrix of eight alpha- and beta-hydroxy acids and six alpha-, beta-, and gamma-amino acids. The reaction products were analyzed by microscopy and a physical stability analyzer to study assembly formation as well as various analytical techniques for chemical analysis. Our results demonstrate assembly formation in depsipeptide systems containing hydrophobic hydroxy acids and indicate that depsipeptide assemblies containing alpha hydroxy acid backbones are significantly more stable than beta analogs. Overall, our results offer an assembly-driven mode of selection for the alpha backbone in present-day biology.