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

Abstract

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.

Keywords: ACE-inhibitory peptides; Mass spectrometry; QSAR; Short-chain peptides; Variable selection.