The origin and evolutionary history of biopolymers has long intrigued scientists. The functions of proteins and nucleic acids in today's biology are tightly intertwined, and we hypothesize that this biological interdependency originated in early chemical evolution with cooperative interactions between proto-peptides and proto-nucleic acids. To explore this hypothesis, researchers from the Center for Chemical Evolution have investigated the production of cationic proto-peptides (depsipeptides and polyesters) in model prebiotic oligomerization reactions and studied their interactions with RNA. The proto-peptides were produced in mild, non-enzymatic oligomerization reactions without activating agents under hydroxy acid-promoted dry-down conditions. The cationic proto-peptides, either as mixtures from the dry-down reactions or synthetically prepared in pure form, can engage in direct, mutually-stabilizing interactions with RNA. Certain cationic proto-peptides significantly increased the thermal stability of folded RNA structures; in turn, RNA reduced the rate of hydrolysis of depsipeptide ester bonds by &gt;30-fold. Intriguingly, we observed that the proteinaceous cationic amino acids (Arg, His, and Lys) oligomerized more extensively and with greater α-amine regioselectivity, and produced oligomers that better stabilized RNA duplex structures, than did analogous sequences containing non-proteinaceous cationic amino acids. Together, our findings provide a purely chemical basis that might have contributed to the selection of the positively charged amino acids found in today’s proteins. Moreover, these results support a model of biopolymer evolution involving a long co-evolutionary history for polypeptide and nucleic acid that began with rudimentary, mutually stabilizing interactions.

What a wonderful (RNA-peptide) world: Mutually stabilizing interactions between proto-peptides and RNA

ACS Spring Meeting 2021

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