ACE-inhibitory peptides from Morchella esculenta: screening, kinetics, and molecular dynamics simulation.

The global prevalence of hypertension has doubled over the past three decades and it is projected to escalate further. Hypertension is a global health concern that is closely linked to angiotensin-converting enzyme (ACE) regulation. Conventional ACE inhibitors demonstrate clinical efficacy; however, their frequent adverse effects underscore an urgent demand for safer therapeutic alternatives. In this context, our study investigates Morchella esculenta as a potential natural source of ACE-inhibitory peptides. The <3 kDa fraction was identified as exhibiting the highest inhibitory activity through the systematic screening of hydrolysates across multiple molecular weight ranges. HPLC-MS/MS analysis identified 163 peptides, of which five were selected for further experiments. Solid-phase synthesis confirmed that LIVPSLPGYAF exhibited the strongest ACE inhibition (IC50 = 50.99 μM). Inhibition kinetics showed LIVPSLPGYAF acted as a mixed-type inhibitor, while GLGPLAQLIWDR and LIFHSFGGTGSGF functioned as competitive inhibitors. Molecular dynamics simulations validated their stable binding to the ACE complex. These findings suggested that Morchella esculenta is a natural source of ACE inhibitory peptides and can potentially be used as a component in functional foods for the treatment of hypertension.