Synthesis of phenylalanyl-arginyl-leucyl-aspartic acid: A model study of the coupling of arginine-terminal tryptic fragments of proteins

Abstract The preparation of l -phenylalanyl- l -arginyl- l -leucyl- l -aspartic acid, through the coupling of benzyloxycarbonyl- l -phenylalanyl- l -arginine and l -leucyl- l -aspartic acid dibenzyl ester, was studied as a model system for the development of optimal conditions for the resynthesis of a 43-residue fragment of staphylococcal nuclease from its tryptic peptides. The coupling reaction was carried out using either water-soluble dicyclohexylcarbodiimide (WS-DCC) in the presence of hydroxysuccinimide (HOSu), WS-DCC without HOSu, or the mixed anhydride method. The tetrapeptide was obtained in a good yield, without racemization, when 1–2 equiv of WS-DCC and 1–1.5 equiv of HOS were used for each equivalent of the acid and amine components.