Analytical and Bioanalytical Chemistry

, Volume 410, Issue 15, pp 3407–3423 | Cite as

Enhancing bioactive peptide release and identification using targeted enzymatic hydrolysis of milk proteins

  • Alice B. Nongonierma
  • Richard J. FitzGerald
Part of the following topical collections:
  1. Discovery of Bioactive Compounds


Milk proteins have been extensively studied for their ability to yield a range of bioactive peptides following enzymatic hydrolysis/digestion. However, many hurdles still exist regarding the widespread utilization of milk protein-derived bioactive peptides as health enhancing agents for humans. These mostly arise from the fact that most milk protein-derived bioactive peptides are not highly potent. In addition, they may be degraded during gastrointestinal digestion and/or have a low intestinal permeability. The targeted release of bioactive peptides during the enzymatic hydrolysis of milk proteins may allow the generation of particularly potent bioactive hydrolysates and peptides. Therefore, the development of milk protein hydrolysates capable of improving human health requires, in the first instance, optimized targeted release of specific bioactive peptides. The targeted hydrolysis of milk proteins has been aided by a range of in silico tools. These include peptide cutters and predictive modeling linking bioactivity to peptide structure [i.e., molecular docking, quantitative structure activity relationship (QSAR)], or hydrolysis parameters [design of experiments (DOE)]. Different targeted enzymatic release strategies employed during the generation of milk protein hydrolysates are reviewed herein and their limitations are outlined. In addition, specific examples are provided to demonstrate how in silico tools may help in the identification and discovery of potent milk protein-derived peptides. It is anticipated that the development of novel strategies employing a range of in silico tools may help in the generation of milk protein hydrolysates containing potent and bioavailable peptides, which in turn may be used to validate their health promoting effects in humans.

Graphical abstract

The targeted enzymatic hydrolysis of milk proteins may allow the generation of highly potent and bioavailable bioactive peptides.


Milk proteins Bioactive peptides Enzyme hydrolysis In silico Quantitative structure activity relationship (QSAR) Peptide identification 



The work described herein was supported by Enterprise Ireland under grant number TC2013-0001. The authors thank Dr. Sara Paolella for her insightful discussions on peptide bond selectivity during enzymatic hydrolysis.

Compliance with ethical standards

Conflicts of interests

The authors declare that they have no conflict of interest.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2017

Authors and Affiliations

  1. 1.Department of Biological Sciences and Food for Health Ireland (FHI)University of LimerickLimerickIreland

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