Molecular interactions, bioavailability, and cellular mechanisms of angiotensin-converting enzyme inhibitory peptides

Food-derived angiotensin-converting enzyme inhibitory (ACEi) peptides have gained substantial interest as potential alternatives to synthetic drugs in the management of hypertension. Peptide size and sequence are two critical factors that determine their potency, bioavailability, and cellular mechanisms. Molecular interaction studies between ACE and ACEi peptides support that potent ACEi peptides are generally composed of hydrophobic, positively charged, and aromatic or cyclic amino acid residues at the third, second, and first position from the C-terminus, respectively. Small peptides containing N-terminal Tyr and/or C-terminal Pro could improve their stability against enterocyte peptidases and, thus, their bioavailability. Different ACEi peptides can reduce aberrant cellular proliferation, excessive inflammation, and oxidative stress but through different mechanisms. Further understanding the structure-activity-bioavailability relationships will help design novel potent ACEi peptides with improved bioavailability and in vivo efficacy.