Strategies for the discovery and identification of food protein-derived biologically active peptides

Background: The widespread application of protein-derived bioactive peptides (BAPs) with health promoting properties in human nutrition is currently limited. This may be due to the fact that several challenges exist in the discovery and identification of BAPs both in vitro and in vivo. Scope and approach: To date, most BAP studies have been conducted following a so-called conventional approach. This is based on the non-targeted release of BAPs in vitro, followed, in certain instances, with their subsequent evaluation in vivo. However, more targeted approaches have recently been described for the release of specific BAPs in a more predictable and efficient manner. These targeted approaches are mostly based on in silico protocols (e.g., peptide cutters, molecular docking, quantitative structure activity relationship (QSAR) models) aimed at predicting the release and/or the bioactivity of specific peptides. Key findings: Targeted approaches have, in certain instances, resulted in the development of particularly potent BAPs/hydrolysates and the discovery of novel BAP sequences. In addition, significant progress has been made in the identification of short peptides, involving the utilisation of multi-stage processes combining various physicochemical, analytical and in silico tools. This has allowed identification of novel sequences which are more relevant to human health from a bioavailability and stability perspective. BAPs have successfully been detected and quantified in human samples (e.g., serum, intestinal contents and urine) using different liquid chromatography-mass spectrometric (LC-MS) methodologies. In addition, human dose-response studies have allowed determination of their in vivo potency and efficacy, which in turn contributes to the development of scientific dossiers for regulatory approval.