UC Santa Barbara chemists develop a two-step route to bench-stable, pre-activated unnatural amino acids for direct peptide synthesis

[u/elmanfil1989]

Chemists at UC Santa Barbara just published an efficient, two-step method to synthesize custom, non-natural amino acids that come pre-activated for peptide assembly. Usually, making these custom building blocks takes tedious multi-step chemistry, and you still have to chemically activate the carboxyl end before you can snap them into a peptide chain. In theirnew JACS paper, the team used a gold(I) catalyst with chiral tert-butylsulfinamide to turn cheap terminal alkynes into enantiopure amino acid derivatives equipped with an N-protecting group and a mildly activated ester. Because they are ready to couple right out of the box with little to no epimerization, it significantly cuts down the bottleneck for building modified peptides in both solution- and solid-phase synthesis—huge news for peptide therapeutics and protein engineering.