Action mechanism of an angiotensin I-converting enzyme inhibitory peptide derived from chicken breast muscle.

In a previous study, we isolated the inhibitory peptide (P4 peptide, Gly-Phe-Hyp-Gly-Thr-Hyp-Gly-Leu-Hyp-Gly-Phe) for angiotensin I-converting enzyme (ACE) from chicken breast muscle extract possessing hypotensive activity for spontaneously hypertensive rats (SHRs). This study was performed to elucidate the peptide's action mechanisms of inhibiting ACE. Intravenous administration of synthetic P4 peptide resulted in significant drops in the blood pressures of SHRs. As Dixon plots indicate, the P4 peptide showed high affinity toward ACE (K(i) = 11.48 microM) and only 10% of the total amount of the P4 peptide was decomposed. The analyses of the relationship between the ACE inhibitory activity and structure of the P4 peptide clarified that Hyp-Gly-Leu-Hyp-Gly-Phe showed a stronger activity (IC50 = 10 microM) than the P4 peptide (IC50 = 46 microM). When Phe at the C-terminus of the P4 peptide was deleted, IC50 changed to 25000 microM, indicating that Phe at the C-terminus of the peptide is very important for ACE inhibitory activity.