(225b) Ester-Mediated Amide Bond Formation and the Prebiotic Origin of Peptides

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. The polycondensation of amino acids is unfavorable in aqueous solution and elevated temperature is necessary.² We report that the addition of α-hydroxy acids can assist the formation of peptide bonds under a relatively mild condition. Hydroxy acids form metastable oligoesters in an oscillating (hot dry/cool wet) system and transit into mixed ester-amide oligomers via the ester-amide exchange reaction.³ Using ion mobility-mass spectrometry and ion mobility-tandem mass spectrometry, we observe the enrichment of amino acids in the oligomers, and the formation of a peptide backbone during the repeated drying-rehydration cycles. The presence of peptide bonds is further confirmed by infrared and 2D NMR spectroscopy. Quantitative NMR analyses indicate that 40% yield of peptide bonds can be achieved. A kinetic model was developed to validate the proposed mechanism and to predict the system behavior under new conditions. In addition, we noticed the reaction ceased due to the loss of lactic acid from evaporation. To enhance the reaction efficiency and to simulate the raining process on the early earth, we further designed a closed system reactor, in which lactic acid and water can be recycled. By integrating the closed system with the oscillation scenario, the efficiency of peptide bond formation increased significantly. Our results demonstrate a simple system exhibiting key features for the emergence of peptides at mild condition.

References

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. Martin, R. B., Free energies and equilibria of peptide bond hydrolysis and formation. Biopolymers 1998, 45 (5), 351-353.
3. Pillon, L. Z.; Utracki, L. A., Compatibilization of polyester/polyamide blends via catalytic ester-amide interchange reaction. Polymer Engineering & Science 1984, 24 (17), 1300-1305.