The invention provides a method of producing a polypeptide having a C-terminal &agr;-carboxamide group. It particularly concerns an enzymatic modification of selected substrate polypeptides which result in cleavage of the substrate polypeptide to form a product peptide with a C-terminal arginine residue having an &agr;-carboxamide group (C-terminal “Arg-NH2”). The method includes contacting an aqueous-based solution including (i) ammonia reagent and (ii) the substrate polypeptide with (iii) clostripain.