Cysteine as peptide precursor and catalyst

Abstract

Prebiotic Chemistry Among amino acids, cysteine is highly reactive as a nucleophile, metal ligand, and participant in redox and radical reactions. These properties make cysteine attractive as a component of prebiotic chemistry, but traditional Strecker synthesis of α-aminonitriles, which can serve as peptide precursors, cannot produce free cysteine. Foden et al. found that a simple acylation of the free amine prevented degradation of cysteine nitrile and enabled synthesis of this cysteine precursor from acetyl dehydroalanine nitrile and a sulfide donor (see the Perspective by Muchowska and Moran). When combined with other proteinogenic α-aminonitriles, acetylcysteine or derivative thiols catalyzed efficient peptide ligation in water. These results highlight how prebiotic synthesis of precursors can also generate function by creating a catalyst for polymerization. Science , this issue p. [865][1]; see also p. [767][2] [1]: /lookup/doi/10.1126/science.abd5680 [2]: /lookup/doi/10.1126/science.abf1698