Iterative Design of a Biomimetic Catalyst for Amino Acid Thioester Condensation.

Herein, the design of a catalyst that combines lessons learned from peptide biosynthesis, enzymes, and organocatalysts is described. The catalyst features a urea scaffold for carbonyl recognition and elements of nucleophilic catalysis. In the presence of 10 mol % of the organocatalyst, the rate of peptide bond formation is accelerated by 10000-fold over the uncatalyzed reaction between Fmoc-amino acid thioesters and amino acid methyl esters.