(255by) Kinetics of Prebiotic Depsipeptide Formation from the Ester-Amide Exchange Reaction

Yu, S. S., Georgia Institute of Technology
Forsythe, J. G., NSF/NASA Center for Chemical Evolution
Krishnamurthy, R., NSF/NASA Center for Chemical Evolution
Fernández, F. M., Georgia Institute of Technology
Hud, N., Georgia Institute of Technology
Schork, F. J., Georgia Institute of Technology
Grover, M. A., Georgia Institute of Technology
In this work, we introduce a kinetic model to study the effectiveness of the ester-mediated amide bond formation under prebiotic conditions. The results of the Miller-Urey experiments and meteorite investigations have provided evidence that amino acids, the building blocks of peptides, existed on the prebiotic earth.1  However, a prebiotically-plausible process for the polymerization of amino acids is still unclear. In our previous study, we found a simple system composed of hydroxy acids and amino acids is capable of forming peptide bonds via esterification and the ester-amide exchange reaction.2To further understand the kinetic behavior of this complex copolymerization, we first designed a closed reactor to monitor the evaporation of water and lactic acid from the reaction mixture. The growth of initial species from a valine and lactic acid mixture was monitored by HPLC-UV/MS. A mathematical model was developed to simulate the reactions and to evaluate the rate constants at different temperatures. Our results reveal that copolymerization between valine and lactic acid is well-characterized by our model and a small number of physical parameters. We found that these reactions can be described by the empirical Arrhenius equation even when the reactions occurred at a dried state. Further calculations for the activation parameters show that the ester-mediated pathway facilitates amide bond formation primarily by having higher activation entropies. These results provide a theoretical framework that illustrates why the ester-mediated pathway for peptide bond formation would have been more favorable on the early Earth than peptide bond formation without the aid of hydroxy acids.

1. (a) Bernstein, M. P.; Dworkin, J. P.; Sandford, S. A.; Cooper, G. W.; Allamandola, L. J., Racemic amino acids from the ultraviolet photolysis of interstellar ice analogues. Nature 2002, 416 (6879), 401-403; (b) Miller, S. L., A production of amino acids under possible primitive earth conditions. Science 1953, 117(3046), 528-529.

2. Forsythe, J. G.; Yu, S.-S.; Mamajanov, I.; Grover, M. A.; Krishnamurthy, R.; Fernández, F. M.; Hud, N. V., Ester-mediated amide bond formation driven by wetâ??dry cycles: A possible path to polypeptides on the prebiotic earth. Angew. Chem. Int. Ed. 2015, 54 (34), 9871-9875.