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Abstract EANA2025-7


Disulfide bonds in the context of peptide formation and the origin of life

Luise Jumpertz (1), Avinash Vicholous Dass (1), Paul Harrison (2), Robert Pascal (1), Vassilissa Vinogradoff (1), Grégoire Danger (1)
(1) Aix-Marseille University, CNRS UMR 7345, PIIM Laboratory -Laboratoire de Physique des Interactions Ioniques et Moléculaires, Marseille, France (2) Department of Chemistry and Chemical Biology, McMaster University, Hamilton, ON, Canada L8S 4M1, Canada


The self-organization of small molecules to oligopeptides and eventually into proteins is still uncertain. Several prebiotic pathways have been proposed to facilitate non-enzymatic peptide bond formation (1–3). In this study, we investigate the role of disulfide bonds as temporary tethers between amino acids to promote peptide bond formation under prebiotic early Earth conditions.

We demonstrate the non-enzymatic formation of a cysteine-cysteine dipeptide via a three-step pathway. Initially, two cysteine molecules form a disulfide-linked dimer, cystine. Upon treatment with a condensing agent (e.g. carbonyl sulfide), cystine undergoes cyclization to yield cyclocystine through intramolecular peptide bond formation. Subsequent reduction of the disulfide bond of the cyclocystine results in the formation of a linear dipeptide composed of two cysteine units.

Using liquid chromatrography-mass spectrometry (LC-MS), we confirm the formation of cyclocystine with both the prebiotic condensing agent carbonyl sulfide (COS) and the non-prebiotic agent 1,1'-carbonyldiimidazole (CDI), activating the amino acid on either the amino group (COS) or the carboxyl group (CDI). Reduction of cyclocystine to the linear cysteine–cysteine dipeptide was achieved using prebiotically plausible agents such as zinc and hydrogen sulfide, as well as the non-prebiotic reductant dithiothreitol (DTT).

These findings support a plausible prebiotic mechanism in which disulfide bonds act as temporary tethers, facilitating intramolecular peptide bond formation and potentially contributing to early peptide synthesis on aqueous environments of the prebiotic Earth.

References

1. Abou Mrad, N. et al. The Prebiotic C‐Terminal Elongation of Peptides Can Be Initiated by N ‐Carbamoyl Amino Acids. Chemistry A European J 23, 7418–7421 (2017).
2. Danger, G., Boiteau, L., Cottet, H. & Pascal, R. The Peptide Formation Mediated by Cyanate Revisited. N -Carboxyanhydrides as Accessible Intermediates in the Decomposition of N -Carbamoylamino Acids. J. Am. Chem. Soc. 128, 7412–7413 (2006).
3. Leman, L., Orgel, L. & Ghadiri, M. R. Carbonyl Sulfide-Mediated Prebiotic Formation of Peptides. Science 306, 283–286 (2004).