Application of Inverse Substrates to Trypsin-Catalyzed Peptide Synthesis

Trypsin-catalyzed peptide synthesis has been studied by using “inverse substrate,” i.e.,p-amidinophenyl ester derived from α-amino acid derivative as an acyl donor component. Inverse substrate can afford acyl trypsin in a very specific manner, liberating the site-specificp-amidinophenyl moiety as the leaving group. Thus a variety of α-amino acid residues which are a part ofp-amidinophenyl ester can be involved in the trypsin-catalyzed coupling reaction. The method has been shown to be successful as expected. In conclusion, the method was proposed as a new procedure which overcomes the disadvantage of enzymatic peptide synthesis.