Screening milk-derived antihypertensive peptides using quantitative structure activity relationship (QSAR) modelling and in vitro/in vivo studies on their bioactivity

In this study, we constructed a quantitative structure activity relationship (QSAR) model of angiotensin I-converting enzyme (ACE) inhibitory tripeptides from published data (R2 = 0.8437; Q2 = 0.649) and applied the model to screen 27 tripeptides derived from cow milk protein sequences. Potential ACE inhibitory tripeptides were synthesised and evaluated in in vitro/in vivo studies. Results showed that ACE inhibitory activities of tripeptides followed the order (p < 0.05): isoleucine-proline-proline (IPP, commercial) > valine-isoleucine-proline (VIP) > isoleucine-valine-proline (IVP) based on concentrations (7.57–49.72 μm) that decreased 50% of ACE activity. Lowering systolic blood pressure (SBP) effect of tripeptides in rats (1.5 mg kg−1 body weight dosage) followed the order according to relative lowering SBP rates: IVP (24%) > IPP (17%) > VIP (12%), consistent with results on mRNA levels of sarcoplasmic reticulum Ca2+, Mg2+ -ATPase gene in rat hearts (p < 0.05). IPP and IVP showed no negative effects on blood glycometabolism.