Enzymatic Fragment Condensation of Side Chain‐Protected Peptides using Subtilisin A in Anhydrous Organic Solvents: A General Strategy for Industrial Peptide Synthesis

Herein, the enzymatic condensation of side chain-protected peptide fragments using subtilisin A in anhydrous organic solvents is described. A screening with dipeptide Cbz-Val-Xxx carboxamidomethyl esters with H-Xxx-Val-NH2 nucleophiles was performed, wherein Xxx stands for every (side chain-protected) amino acid residue. Finally, it was demonstrated that it is feasible to enzymatically condense larger peptide fragments (up to the 10-mer level) bearing multiple side chain-protecting groups with very high conversion.