Strategies for the discovery, identification and validation of milk protein-derived bioactive peptides

•Milk bioactive peptides (BAPs) have potential for the management of human diseases.•Drug discovery approaches may be used to study milk BAPs.•The low potency and occurrence level of BAPs in humans is a challenge.•A reversed workflow approach from in vivo to in vitro evaluation is proposed.

BackgroundThe workflow used for the discovery of novel milk protein-derived bioactive peptides (BAPs) has significantly evolved over the past number of years. Many of the approaches currently described in the literature for the study of milk protein-derived BAPs have taken similar routes as those conventionally used in drug discovery. However, because milk protein-derived BAPs are prepared from dietary sources and in a food-grade manner, they differ from drugs in that they are generally present in a complex mixture as opposed to drug active compounds which are generally synthetically produced, having a relatively high level of purity.Scope and approachThis review assesses the utilisation of drug discovery methods for the identification of novel milk protein-derived BAPs. Different methods relevant to drug discovery have already proven effective for the discovery of new BAPs from milk proteins.Key findings and conclusionsHowever, reversing the workflow, starting from peptide identification in vivo to in vitro screening followed by conventional drug discovery approaches may have several merits. These include (a) the design of more targeted studies, (b) the development of novel approaches for the generation of milk protein hydrolysates and (c) the discovery of milk BAPs which may be bioavailable in humans. These BAPs may find applications in the commercial generation of dietary ingredients with health promoting effects in humans.