Rearrangement of terminal amino acid residues in peptides by protease-catalyzed intramolecular transpeptidation.

Protease-catalyzed rearrangements of amino acid residues in peptides are observed during enzymatic digestion of proteins. When two enzyme-specific cleavage sites are within one or two residues of each other in the protein sequence, only one of the two sites usually is hydrolyzed by the protease, resulting in a peptide that contains an extra cleavage site near one of its termini. It is observed that in this type of peptide, the residues between the two cleavage sites often rearrange from one terminus of the peptide to the other terminus, catalyzed by the protease that created the peptide. It is proposed that the rearrangement is caused by protease-catalyzed intramolecular transpeptidation through a cyclic peptide intermediate. Several cases of this type of rearrangement were observed for different peptides generated by different proteases, indicating that this type of rearrangement is a general phenomenon occurring during enzymatic digestion of proteins.