Reversible Cystine Disulfide Scaffolding Enables Carbonyl Sulfide-Mediated Intramolecular Peptide Bond Formation via Cyclocystine: Implications for Prebiotic Chemistry.

Treatment of cystine (the disulfide-linked dimer of cysteine) with carbonyl sulfide (COS) results in the formation of cyclocystine, which upon reduction yields the Cys-Cys dipeptide. These findings demonstrate a role for the cystine disulfide bond as a molecular scaffold that favors intramolecular peptide bond formation. In contrast, no dipeptide formation was observed when cysteine was subjected to the same reaction conditions, further supporting the importance of the disulfide scaffold in promoting this transformation. The possible relevance of these observations to selective prebiotic polymerization is discussed. The production of cyclocystine was established using LC-Orbitrap mass spectrometry as well as proton and COSY NMR spectroscopy, while formation of Cys-Cys dipeptide following reduction was confirmed by LC-Orbitrap mass spectrometry and comparison with a synthetic standard. Further confirmation of the formation of cyclocystine and the dipeptide product was obtained through benzoylation-based derivatization.