Inhibition of prolyl endopeptidase by synthetic peptide fragments of human beta-casein.

It has been suggested that peptide inhibitors of prolyl endopeptidase (PEP) may act as anti-amnestic agents. In the hope of finding PEP inhibitors in milk proteins, we synthesized a total of 37 human beta-casein peptide fragments containing proline residues. It was found that the peptides with PEP inhibition activity in vitro were located in the region of amino acid residues 49-59 of human beta-casein. The most potent inhibitor was Ile-Tyr-Pro-Phe-Val-Glu-Pro-Ile (IC50 = 8 microM).