Inhibition of Angiotensin-converting Enzyme by Synthetic Peptides of Human β-Casein

Abstract

The possible roles of caseins as exorphins, immunostimulants and hypotensive agents have recently been suggested by several groups. In an attempt to prove the existence and to elucidate the physiological significance of peptide inhibitors of angiotensin-converting enzyme (ACE) in milk proteins, we synthesized a total of 69 peptide fragments of human ^-casein, in which a proline residue was placed at the C-terminus for the ACE inhibitory activity. It was found that the peptides with potent inhibitory activity in vitro were located in the region of amino acid residues 39 ~ 52 of human p- casein. All the peptides within this sequence (39~52) had potent ACE inhibitory activity. The most potent inhibitor was a decapeptide, Ser-Phe-Gln-Pro-Gln-Pro-Leu-Ile-Tyr-Pro (IC₅₀ = 1.4 μm), which was also active in vivo.