Bioaccessibility of novel antihypertensive short-chain peptides in goat milk using the INFOGEST static digestion model by effect-directed assays

Short-chain peptides (SCPs, 2-4 amino acids) offer potential health benefits. A customized workflow was designed to screen SCPs in goat milk during INFOGEST digestion in vitro and 186 SCPs were preliminarily identified. Based on a two-terminal position numbering method and genetic algorithm combined with a support vector machine, 22 SCPs with predicted IC50 values less than 10 μM were obtained using a quantitative structure-activity relationship (QSAR) model with satisfactory fitting and predictive capacity (R2, RMSE, Q2, and R2pre of 0.93, 0.27, 0.71, and 0.65, respectively). Four novel antihypertensive SCPs were confirmed by testing in vitro and molecular docking analysis, and their quantification results (0.06 to 1.53 mg L-1) suggested distinct metabolic fates. This study facilitated the discovery of unknown potential food-derived antihypertensive peptides and the understanding of bioaccessible peptides during digestion.