Discovery of novel angiotensin-converting enzyme inhibitory peptides by in silico and in vitro studies.

Hypertension represents a crucial risk factor in the development of cardiovascular diseases, including heart failure, stroke, coronary heart disease and myocardial infarction. Currently, synthetic angiotensin-converting enzyme (ACE) inhibitors are an important first-line treatment for hypertension. However, these synthetic ACE inhibitors often produce side effects in clinical application, such as cough, gustatory disturbance and skin rash. Thus, it is urgent to find safe and effective ACE inhibitors for the treatment of hypertension. Therefore, a series of ACE inhibitory peptides were studied using computational approaches. Initially, a reliable 3D-QSAR model was derived based on CoMFA (R cv 2 = 0.660, R pred 2 = 0.6674) and CoMSIA (R cv 2 = 0.646, R pred 2 = 0.6451) methods. Furthermore, molecular docking was also employed to explore the binding mode of the inhibitory peptides at the active site of ACE. At the same time, the ligand-receptor binding characteristics are consistent with the contour map information. Taken together, the derived 3D-QSAR and molecular docking results would offer trustworthy clues for further optimization of this series of ACE inhibitory peptides. Finally, three novel tri-peptides are designed as prospective ACE inhibitors, and the predicted activities by developed 3D-QSAR models, binding affinity by molecular docking, the experimental activity by DOJINDO ACE Kit-WST reagent box all show effective inhibition on ACE.