Prebiotic Environments with Mg(2+) and Thiophilic Metal Ions Increase the Thermal Stability of Cysteine and Non-cysteine Peptides

[Image: see text] Wet–dry cycles driven by heating to high temperatures are frequently invoked for the prebiotic synthesis of peptides. Similarly, iron–sulfur clusters are often cited as an example of an ancient catalyst that helped prune early chemical systems into metabolic-like pathways. Because extant iron–sulfur clusters are metallocofactors of protein enzymes and nearly ubiquitous across biology, a reasonable hypothesis is that prebiotic iron–sulfur peptides formed on the early Earth. However, iron–sulfur clusters are coordinated by multiple cysteine residues, and the stability of cysteines to the heat steps of wet–dry cycles has not been determined. It, therefore, has remained unclear if the peptides needed to stabilize the formation of iron–sulfur clusters could have formed. If not, then iron–sulfur-dependent activity may have emerged later, when milder, more biological-like peptide synthesis machinery took hold. Here, we report the thermal stability of cysteine-containing peptides. We show that temperatures of 150 °C lead to the rapid degradation of cysteinyl peptides. However, the presence of Mg(2+) at environmentally reasonable concentrations leads to significant protection. Thiophilic metal ions also protect against degradation at 150 °C but require concentrations not frequently observed in the environment. Nevertheless, cysteine-containing peptides are stable at lower, prebiotically plausible temperatures in seawater, carbonate lake, and ferrous lake conditions. The data are consistent with the persistence of cysteine-containing peptides on the early Earth in environments rich in metal ions. High concentrations of Mg(2+) are common intra- and extra-cellularly, suggesting that the protection afforded by Mg(2+) may reflect conditions that were present on the prebiotic Earth.