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

Abstract

17Background: The workflow used for the discovery of novel milk protein-derived bioactive 18 peptides (BAPs) has significantly evolved over the past number of years. Many of the 19 approaches currently described in the literature for the study of milk protein-derived BAPs have 20 taken similar routes as those conventionally used in drug discovery. However, because milk 21 protein-derived BAPs are prepared from dietary sources and in a food-grade manner, they differ 22 from drugs in that they are generally present in a complex mixture as opposed to drug active 23 compounds which are generally synthetically produced, having a relatively high level of purity.

Peptides: Production, bioactivity, functionality, and applications

“…BIOPEP, a database mainly focused on peptides from food, is generally employed to determine the occurrence frequency of embedded bioactive peptides in the primary structure of the food proteins of interest (Udenigwe, 2014;Lacroix and Li-Chan, 2012). Peptide cutter programs (e.g., ExPASy) are used to generate peptide profiles in silico from specific primary protein structures using enzymes of known specificity (Udenigwe et al, 2013;Nongonierma and FitzGerald, 2016a). Peptide cutters have been also employed to assay the potential cleavage by gastrointestinal tract enzymes of bioactive peptides obtained experimentally .…”

“…Examples in the literature include studies on ACE as well as DPP-IV inhibitory peptides (Lin et al, 2017;Nongonierma et al 2014). Thus, in silico tools may expedite the discovery and production of bioactive peptides from food proteins, although they still have some limitations (e.g., do not consider secondary, tertiary and quaternary structures of proteins to predict cleavage sites; and assume enzymes with stringent substrate specificity, which is not always the case in food applications where complex proteaseproteins interactions occur) (Li-Chan, 2015;Nongonierma and FitzGerald, 2016a;Udenigwe, 2014).…”

“…Although there have been several in vivo investigations proving the bioactivity of peptides and hydrolysates in animal models, the results of these studies cannot be confidently generalized to humans due to the disagreement between human and animal studies. Nongonierma and FitzGerald (2016a) explained that the discrepancy between human and animal studies could be caused by two major reasons, i.e., biological differences between humans and animals and differences in experimental set-up (Nongonierma and FitzGerald, 2016b). In addition to their application in functional foods and nutraceuticals, bioactive peptides and hydrolysates are used to produce drugs and cosmetics.…”

Learnings from quantitative structure–activity relationship (QSAR) studies with respect to food protein-derived bioactive peptides: a review

“…Various publicly available BAP databases have been listed in recent reviews. 15,19 BIOPEP, for example, is a database which is commonly employed for the study of dietary peptides.…”

Novel angiotensin-converting enzyme inhibitory peptides from caseins and whey proteins of goat milk

“…Such peptides are being identified in dairy protein hydrolysates and shown to possess opioid, immune-modulatory, antimicrobial, antithrombotic, growth stimulating or antihypertensive properties [1], [2]. The milk protein-derived bioactive peptides have the potential to be formulated into foods to provide their health promoting effects in human.…”