Discovery of novel angiotensin-converting enzyme inhibitory peptides in vinegar through peptidomics and molecular docking analysis

The inhibitory activity of different ultrafiltration fractions derived from the water-soluble extract of Zhenjiang aromatic vinegar (ZAV) on angiotensin-converting enzyme (ACE) was evaluated, and endogenous peptides with potential ACE inhibition were screened through ultrafiltration and reversed-phase high-performance liquid chromatography (RP–HPLC) coupled with ACE inhibition detection. Several novel ACE inhibitory peptides were identified using a peptidomic approach based on nanoLC-MS/MS. A total of 710 peptides were identified in the RP–HPLC fractions. Additionally, four novel peptides with potential ACE inhibitory activity were identified: FPEQPP, VVPPGHPV, FPPQQP, and YGRGPIE, with IC 50 values of 3.7 ± 0.1 μM, 3.3 ± 0.4 μM, 1.6 ± 0.2 μM, and 5.9 ± 0.2 μM, respectively. Of these novel peptides, FPPQQP was the peptide with the most potent antihypertensive activity, which acted as a strong inhibitor of ACE through molecular docking. These findings suggest that integrating peptidomics and molecular docking provides an efficient strategy for the rapid investigation of ACE inhibitory peptides in food matrices.