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

Analytical and Bioanalytical Chemistry

Volumn 410, Issue 15, 2018, Pages 3407-3423

  Nongonierma, Alice B ^a   FitzGerald, Richard J ^a  

^a UNIVERSITY OF LIMERICK   (Ireland)

Author keywords

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

Indexed keywords

COMPUTATIONAL CHEMISTRY; DESIGN OF EXPERIMENTS; ENZYMATIC HYDROLYSIS; HEALTH; HYDROLYSIS; PEPTIDES; STRUCTURES (BUILT OBJECTS);

BIOACTIVE PEPTIDES; ENZYME HYDROLYSIS; IN-SILICO; MILK PROTEIN; PEPTIDE IDENTIFICATION; QUANTITATIVE STRUCTURE-ACTIVITY RELATIONSHIPS;

PROTEINS;

MILK PROTEIN; PEPTIDE; PROTEIN HYDROLYSATE;

AMINO ACID SEQUENCE; ANIMAL; BOVINE; CHEMISTRY; COMPUTER SIMULATION; HYDROLYSIS; MILK;

AMINO ACID SEQUENCE; ANIMALS; CATTLE; COMPUTER SIMULATION; HYDROLYSIS; MILK; MILK PROTEINS; PEPTIDES; PROTEIN HYDROLYSATES;

EID: 85038357499     PISSN: 16182642     EISSN: 16182650     Source Type: Journal    
DOI: 10.1007/s00216-017-0793-9     Document Type: Review

References (138)

1. Korhonen H, Pihlanto A (2006) Bioactive peptides: production and functionality. Int Dairy J 16:945–160
2. Anusha R, Bindhu OS. Bioactive peptides from milk. In: Gigli I, Ed. Milk Proteins - From Structure to Biological Properties and Health Aspects. Rijeka: InTech. DOI: 10.5772/62993. Available from: https://www.intechopen.com/books/milk-proteins-from-structure-to-biological-properties-and-health-aspects/bioactive-peptides-from-milk; 2016.
3. Nongonierma AB, O’Keeffe MB, RJ FG. Milk Protein Hydrolysates and Bioactive Peptides. Advanced Dairy Chemistry. New York: Springer; 2016. p. 417–82.
4. Nongonierma AB, FitzGerald RJ. Biofunctional properties of caseinophosphopeptides in the oral cavity. Caries Res. 2012;46:234–67.
5. Nongonierma AB, FitzGerald RJ. The scientific evidence for the role of milk protein-derived bioactive peptides in humans: A review. J Funct Foods. 2015;640:640–56.
6. Nongonierma AB, FitzGerald RJ. Bioactive properties of milk proteins in humans: A review. Peptides. 2015;73:20–34.
7. Boutrou R, Henry G, Sanchez-Rivera L. On the trail of milk bioactive peptides in human and animal intestinal tracts during digestion: A review. Dairy Sci Technol. 2015:1–15.
8. Egger L, Ménard O. Update on bioactive peptides after milk and cheese digestion. Curr Opin Food Sci. 2017;14:116–21.
9. Kaiser S, Martin M, Lunow D, Rudolph S, Mertten S, Möckel U, et al. Tryptophan-containing dipeptides are bioavailable and inhibit plasma human angiotensin-converting enzyme in vivo. Int Dairy J. 2016;52:107–14.
10. Foltz M, Meynen EE, Bianco V, van Platerink C, Koning TMMG, Kloek J. Angiotensin converting enzyme inhibitory peptides from a lactotripeptide-enriched milk beverage are absorbed intact into the circulation. J Nutr. 2007;137:953–8.
11. Caira S, Pinto G, Vitaglione P, Dal Piaz F, Ferranti P, Addeo F. Identification of casein peptides in plasma of subjects after a cheese-enriched diet. Food Res Int. 2016;84:108–12.
12. Boutrou R, Gaudichon C, Dupont D, Jardin J, Airinei G, Marsset-Baglieri A, et al. Sequential release of milk protein-derived bioactive peptides in the jejunum in healthy humans. Am J Clin Nutr. 2013;97:1314–23.
13. Pripp AH. Initial proteolysis of milk proteins and its effect on formation of ACE-inhibitory peptides during gastrointestinal proteolysis: a bioinformatic, in silico, approach. Eur Food Res Technol. 2005;221:712–6.
14. Udenigwe CC. Bioinformatics approaches, prospects and challenges of food bioactive peptide research. Trends Food Sci Technol. 2014;36:137–43.
15. Nongonierma AB, FitzGerald RJ. Strategies for the discovery, identification and validation of milk protein-derived bioactive peptides. Trends Food Sci Technol. 2016;50:26–43.
16. Li-Chan EC. Bioactive peptides and protein hydrolysates: Research trends and challenges for application as nutraceuticals and functional food ingredients. Curr Opin Food Sci. 2015;1:28–37.
17. Contreras MM. Hernández-Ledesma B, Amigo L, Martín-Álvarez PJ, Recio I. Production of antioxidant hydrolyzates from a whey protein concentrate with thermolysin: Optimization by response surface methodology. LWT Food Sci Technol. 2011;44:9–15.
18. van der Ven C, Gruppen H, de Bont DBA, Voragen AGJ. Optimization of the angiotensin converting enzyme inhibition by whey protein hydrolysates using response surface methodology. Int Dairy J. 2002;12:813–20.
19. Iwaniak A, Minkiewicz P, Darewicz M, Protasiewicz M, Mogut D. Chemometrics and cheminformatics in the analysis of biologically active peptides from food sources. J Funct Foods. 2015;16:334–51.
20. Udenigwe CC, Gong M, Wu S. In silico analysis of the large and small subunits of cereal RuBisCO as precursors of cryptic bioactive peptides. Process Biochem. 2013;48:1794–9.
21. Udenigwe CC. Towards rice bran protein utilization: In silico insight on the role of oryzacystatins in biologically-active peptide production. Food Chem. 2016;191:135–8.
22. Wang T-Y, Hsieh C-H, Hung C-C, Jao C-L, Lin P-Y, Hsieh Y-L, et al. A study to evaluate the potential of an in silico approach for predicting dipeptidyl peptidase-IV inhibitory activity in vitro of protein hydrolysates. Food Chem. 2017;234:431–8.
23. Lacroix IME, Li-Chan ECY. Evaluation of the potential of dietary proteins as precursors of dipeptidyl peptidase (DPP)-IV inhibitors by an in silico approach. J Funct Foods. 2012;4:403–22.
24. Minkiewicz P, Dziuba J, Michalska J. Bovine meat proteins as potential precursors of biologically active peptides - a computational study based on the BIOPEP database. Food Sci Technol Int. 2011;17:39–45.
25. Vercruysse L, Van Camp J, Smagghe G. ACE inhibitory peptides derived from enzymatic hydrolysates of animal muscle protein: a review. J Agric Food Chem. 2005;53:8106–15.
26. Gu Y, Majumder K, Wu J. QSAR-aided in silico approach in evaluation of food proteins as precursors of ACE inhibitory peptides. Food Res Int. 2011;44:2465–74.
27. Fu Y, Wu W, Zhu M, Xiao Z. In silico assessment of the potential of patatin as a precursor of bioactive peptides. J Food Biochem. 2016;40:366–70.
28. Rajendran SRCK, Mason B, Udenigwe CC. Peptidomics of peptic digest of selected potato tuber proteins: Post-translational modifications and limited cleavage specificity. J Agric Food Chem. 2016;64:2432–7.
29. Nongonierma AB, FitzGerald RJ. Strategies for the discovery and identification of food protein-derived biologically active peptides. Trends Food Sci Technol. 2017;69:289-305.
30. Capriotti AL, Cavaliere C, Piovesana S, Samperi R, Laganà A. Recent trends in the analysis of bioactive peptides in milk and dairy products. Anal Bioanal Chem. 2016;408:2677–85.
31. El-Salam MA, El-Shibiny S. Bioactive peptides of buffalo, camel, goat, sheep, mare, and yak milks and milk products. Food Rev Int. 2013;29:1–23.
32. Mati A, Senoussi-Ghezali C, Zennia SSA, Almi-Sebbane D, El-Hatmi H, Girardet J-M. Dromedary camel milk proteins, a source of peptides having biological activities–A review. Int Dairy J. 2017;73:25–37.
33. Vincenzetti S, Pucciarelli S, Polzonetti V, Polidori P. Role of proteins and of some bioactive peptides on the nutritional quality of donkey milk and their impact on human health. Beverages. 2017;3:34.
34. Agarwal S, Beausire RLW, Patel S, Patel H. Innovative uses of milk protein concentrates in product development. J Food Sci. 2015;80:A23–A9.
35. de la Fuente MA, Hemar Y, Tamehana M, Munro PA, Singh H. Process-induced changes in whey proteins during the manufacture of whey protein concentrates. Int Dairy J. 2002;12:361–9.
36. Le Maux S, Nongonierma AB, FitzGerald RJ. Peptide composition and dipeptidyl peptidase IV inhibitory properties of β-lactoglobulin hydrolysates having similar extents of hydrolysis while generated using different enzyme-to-substrate ratios. Food Res Int. 2017;99:84–90.
37. Nongonierma AB, FitzGerald RJ. Tryptophan-containing milk protein-derived dipeptides inhibit xanthine oxidase. Peptides. 2012;37:263–72.
38. Kalyankar P, Zhu Y, O’Keeffe M, O’Cuinn G, RJ FG. Substrate specificity of glutamyl endopeptidase (GE): Hydrolysis studies with a bovine α-casein preparation. Food Chem. 2013;136:501–12.
39. Lacroix IM, Li-Chan ECY. Inhibition of dipeptidyl peptidase (DPP)-IV and α-glucosidase activities by pepsin-treated whey proteins. J Agric Food Chem. 2013;61:7500–6.
40. Fan F, Tu M, Liu M, Shi P, Wang Y, Wu D, et al. Isolation and characterization of lactoferrin peptides with stimulatory effect on osteoblast proliferation. J Agric Food Chem. 2017;65:7179–85.
41. Cheison SC, Schmitt M, Leeb E, Letzel T, Kulozik U. Influence of temperature and degree of hydrolysis on the peptide composition of trypsin hydrolysates of β-lactoglobulin: Analysis by LC–ESI-TOF/MS. Food Chem. 2010;121:457–67.
42. Nongonierma AB, FitzGerald RJ. Enzymes exogenous to milk in dairy technology | Proteinases. In: Fuquay JW, editor. Encyclopedia of Dairy Sciences. 2nd ed. San Diego: Academic Press; 2011. p. 289–96.
43. Tavano OL. Protein hydrolysis using proteases: an important tool for food biotechnology. J Mol Catal B Enzym. 2013;90:1–11.
44. Stepaniak L. Dairy enzymology. Int J Dairy Technol. 2004;57:153–71.
45. Sanchón J, Fernández-Tomé S, Miralles B, Hernández-Ledesma B, Tomé D, Gaudichon C, et al. Protein degradation and peptide release from milk proteins in human jejunum. Comparison with in vitro gastrointestinal simulation. Food Chem. 2018;239:486–94.
46. Lemes AC, Sala L, Ores JDC, ARC B, Egea MB, Fernandes KF. A review of the latest advances in encrypted bioactive peptides from protein-rich waste. Int J Mol Sci. 2016;17:950.
47. Toldrá F, Reig M, Aristoy MC, Mora L. Generation of bioactive peptides during food processing. Food Chem. 2017.
48. Mullally MM, O'Callaghan DM, FitzGerald RJ, Donnelly W, Dalton JP. Proteolytic and peptidolytic activities in commercial pancreatic protease preparations and their relationship to some whey protein hydrolyzate characteristics. J Agric Food Chem. 1994;42:2973–81.
49. Spellman D, Kenny P, O'Cuinn G, FitzGerald RJ. Aggregation properties of whey protein hydrolysates generated with Bacillus licheniformis proteinase activities. J Agric Food Chem. 2005;53:1258–65.
50. Kilcawley KN, Wilkinson MG, Fox PF. Determination of key enzyme activities in commercial peptidase and lipase preparations from microbial or animal sources. Enzym Microb Technol. 2002;31:310–20.
51. Merz M, Eisele T, Berends P, Appel D, Rabe S, Blank I, et al. Flavourzyme, an enzyme preparation with industrial relevance: Automated nine-step purification and partial characterization of eight enzymes. J Agric Food Chem. 2015;63:5682–93.
52. Merz M, Appel D, Berends P, Rabe S, Blank I, Stressler T, et al. Batch-to-batch variation and storage stability of the commercial peptidase preparation Flavourzyme in respect of key enzyme activities and its influence on process reproducibility. Eur Food Res Technol. 2016;242:1005–12.
53. Butré CI, Sforza S, Gruppen H, Wierenga PA. Determination of the influence of substrate concentration on enzyme selectivity using whey protein isolate and Bacillus licheniformis protease. J Agric Food Chem. 2014;62:10230–9.
54. Butré CI, Sforza S, Wierenga PA, Gruppen H. Determination of the influence of the pH of hydrolysis on enzyme selectivity of Bacillus licheniformis protease towards whey protein isolate. Int Dairy J. 2015;44:44–53.
55. NCBI. https://www.ncbi.nlm.nih.gov/protein/. Accessed 19 Sept 2017.
56. UniProt. www.uniprot.org/. Accessed 19 Sept 2017.
57. Dziuba J, Minkiewicz P, Nałecz D, Iwaniak A. Database of biologically active peptide sequences. Food/Nahrung. 1999;43:190–5.
58. BIOPEP. http://www.uwm.edu.pl/biochemia/index.php/en/biopep. Accessed 18 Sept 2017.
59. MBPDB. http://mbpdb.nws.oregonstate.edu. Accessed 19 Sept 2017.
60. Nielsen SD, Beverly RL, Qu Y, Dallas DC. Milk bioactive peptide database: A comprehensive database of milk protein-derived bioactive peptides and novel visualization. Food Chem. 2017;232:673–82.
61. Vermeirssen V, van der Bent A, Van Camp J, van Amerongen A, Verstraete W. A quantitative in silico analysis calculates the angiotensin I converting enzyme (ACE) inhibitory activity in pea and whey protein digests. Biochimie. 2004;86:231–9.
62. Dziuba M, Dziuba B, Iwaniak A. Milk proteins as precursors of bioactive peptides. Acta Sci Pol Technol Aliment. 2009;8:71–90.
63. Nongonierma AB, FitzGerald RJ. An in silico model to predict the potential of dietary proteins as sources of dipeptidyl peptidase IV (DPP-IV) inhibitory peptides. Food Chem. 2014;165:489–98.
64. Dziuba J, Iwaniak A, Minkiewicz P. Computer-aided characteristics of proteins as potential precursors of bioactive peptides. Polimery. 2003;48:50–3.
65. Tulipano G, Sibilia V, Caroli AM, Cocchi D. Whey proteins as source of dipeptidyl dipeptidase IV (dipeptidyl peptidase-4) inhibitors. Peptides. 2011;32:835–8.
66. Dziuba B, Dziuba M. New milk protein-derived peptides with potential antimicrobial activity: An approach based on bioinformatic studies. Int J Mol Sci. 2014;15:14531–45.
67. Nongonierma AB, FitzGerald RJ. Dipeptidyl peptidase IV inhibitory and antioxidative properties of milk-derived dipeptides and hydrolysates. Peptides. 2013;39:157–63.
68. Nongonierma AB, FitzGerald RJ. Inhibition of dipeptidyl peptidase IV (DPP-IV) by proline containing peptides. J Funct Foods. 2013;5:1909–17.
69. ExPASy. http://web.expasy.org/peptide_cutter/peptidecutter_enzymes.html#Peps. Accessed 18 Sept 2017.
70. MEROPS. https://www.ebi.ac.uk/merops/. Accessed 18 Sept 2017.
71. O’Loughlin IB, Murray BA, Kelly PM, FitzGerald RJ, Brodkorb A. Enzymatic hydrolysis of heat-induced aggregates of whey protein isolate. J Agric Food Chem. 2012;60:4895–904.
72. Vorob’ev MM, Butré CI, Sforza S, Wierenga PA, Gruppen H. Demasking kinetics of peptide bond cleavage for whey protein isolate hydrolyzed by Bacillus licheniformis protease. J Mol Catal B: Enzym. 2017.
73. Panchaud A, Affolter M, Kussmann M. Mass spectrometry for nutritional peptidomics: How to analyze food bioactives and their health effects. J Proteome. 2012;75:3546–59.
74. Sánchez-Rivera L, Martínez-Maqueda D, Cruz-Huerta E, Miralles B, Recio I. Peptidomics for discovery, bioavailability and monitoring of dairy bioactive peptides. Food Res Int. 2014;63(Part B):170–81.
75. Nongonierma AB, Le Maux S, Hamayon J, FitzGerald RJ. Strategies for the release of dipeptidyl peptidase IV (DPP-IV) inhibitory peptides in an enzymatic hydrolyzate of α-lactalbumin. Food Funct. 2016;7:3437–43.
76. Kalyankar P, Zhu Y, O’Cuinn G, FitzGerald RJ. Investigation of the substrate specificity of glutamyl endopeptidase using purified bovine β-casein and synthetic peptides. J Agric Food Chem. 2013;61:3193–204.
77. Norris R, Poyarkov A, O’Keeffe MB, FitzGerald RJ. Characterization of the hydrolytic specificity of Aspergillus niger derived prolyl endoproteinase on bovine β-casein and determination of ACE inhibitory activity. Food Chem. 2014;156:29–36.
78. Norris R, O’Keeffe MB, Poyarkov A, FitzGerald RJ. Peptide identification and angiotensin converting enzyme (ACE) inhibitory activity in prolyl endoproteinase digests of bovine αs-casein. Food Chem. 2015;188:210–7.
79. Tulipano G, Faggi L, Nardone A, Cocchi D, Caroli AM. Characterization of the potential of β-lactoglobulin and α-lactalbumin as sources of bioactive peptides affecting incretin function: in silico and in vitro comparative studies. Int Dairy J. 2015;48:66–72.
80. Guinane CM, Kent RM, Norberg S, O'Connor PM, Cotter PD, Hill C, et al. Generation of the antimicrobial peptide caseicin A from casein by hydrolysis with thermolysin enzymes. Int Dairy J. 2015;49:1–7.
81. Zhang Y, Chen R, Zuo F, Ma H, Zhang Y, Chen S. Comparison of dipeptidyl peptidase IV-inhibitory activity of peptides from bovine and caprine milk casein by in silico and in vitro analyses. Int Dairy J. 2016;53:37–44.
82. Nongonierma AB, Paolella S, Mudgil P, Maqsood S, FitzGerald RJ. Dipeptidyl peptidase IV (DPP-IV) inhibitory properties of camel milk protein hydrolysates generated with trypsin. J Funct Foods. 2017;34:49–58.
83. Nongonierma AB, FitzGerald RJ. Susceptibility of milk protein-derived peptides to dipeptidyl peptidase IV (DPP-IV) hydrolysis. Food Chem. 2014;145:845–52.
84. Butré CI, Buhler S, Sforza S, Gruppen H, Wierenga PA. Spontaneous, non-enzymatic breakdown of peptides during enzymatic protein hydrolysis. Biochim Biophysica Acta (BBA) - Proteins Proteomics. 2015;1854:987–94.
85. Pina AS, Roque ACA. Studies on the molecular recognition between bioactive peptides and angiotensin-converting enzyme. J Mol Recognit. 2009;22:162–8.
86. Norris R, Casey F, FitzGerald RJ, Shields DC, Mooney C. Predictive modeling of angiotensin converting enzyme inhibitory dipeptides. Food Chem. 2012;133:1349–54.
87. Pripp AH. Docking and virtual screening of ACE inhibitory dipeptides. Eur Food Res Technol. 2007;225:589–92.
88. Nongonierma AB, Mooney C, Shields DC, FitzGerald RJ. Inhibition of dipeptidyl peptidase IV and xanthine oxidase by amino acids and dipeptides. Food Chem. 2013;141:644–53.
89. Vukic VR, Vukic DV, Milanovic SD, Ilicic MD, Kanuric KG, Johnson MS. In silico identification of milk antihypertensive di- and tripeptides involved in angiotensin I–converting enzyme inhibitory activity. Nutr Res. 2017;46:22–30.
90. Nongonierma AB, Mooney C, Shields DC, FitzGerald RJ. In silico approaches to predict the potential of milk protein-derived peptides as dipeptidyl peptidase IV (DPP-IV) inhibitors. Peptides. 2014;57:43–51.
91. Fernández-Tomé S, Martínez-Maqueda D, Girón R, Goicoechea C, Miralles B, Recio I. Novel peptides derived from αs1-casein with opioid activity and mucin stimulatory effect on HT29-MTX cells. J Funct Foods. 2016;25:466–76.
92. Nongonierma AB, FitzGerald RJ. Learnings from quantitative structure-activity relationship (QSAR) studies with respect to food protein-derived bioactive peptides: A review. RSC Adv. 2016;6:75400–13.
93. Udenigwe CC, Li H, Aluko RE. Quantitative structure–activity relationship modeling of renin-inhibiting dipeptides. Amino Acids. 2011;42:1379–86.
94. Wu J, Aluko RE. Quantitative structure-activity relationship study of bitter di- and tri-peptides including relationship with angiotensin I-converting enzyme inhibitory activity. J Pept Sci. 2007;13:63–9.
95. Wu J, Aluko RE, Nakai S. Structural requirements of angiotensin I-converting enzyme inhibitory peptides: Quantitative structure-activity relationship study of di-and tripeptides. J Agric Food Chem. 2006;54:732–8.
96. Wang J-H, Liu Y-L, Ning J-H, Yu J, Li X-H, Wang F-X. Is the structural diversity of tripeptides sufficient for developing functional food additives with satisfactory multiple bioactivities? J Mol Struct. 2013;1040:164–70.
97. Pripp AH, Isaksson T, Stepaniak L, Sørhaug T. Quantitative structure-activity relationship modeling of ACE-inhibitory peptides derived from milk proteins. Eur Food Res Technol. 2004;219:579–83.
98. Nongonierma AB, FitzGerald RJ. Structure activity relationship modeling of milk protein-derived peptides with dipeptidyl peptidase IV (DPP-IV) inhibitory activity. Peptides. 2016;79:1–7.
99. Maruyama S, Miyoshi S, Kaneko T, Tanaka H. Angiotensin I-converting enzyme inhibitory activities of synthetic peptides related to the tandem repeated sequence of a maize endosperm protein. Agric Biol Chem. 1989;53:1077–81.
100. Mooney C, Haslam NJ, Pollastri G, Shields DC. Towards the improved discovery and design of functional peptides: common features of diverse classes permit generalized prediction of bioactivity. PLoS One. 2012;7:e45012.
101. Zenezini Chiozzi R, Capriotti AL, Cavaliere C, La Barbera G, Piovesana S, Samperi R, et al. Purification and identification of endogenous antioxidant and ACE-inhibitory peptides from donkey milk by multidimensional liquid chromatography and nanoHPLC-high resolution mass spectrometry. Anal Bioanal Chem. 2016;408:5657–66.
102. Rani S, Pooja K, Pal GK. Exploration of potential angiotensin converting enzyme inhibitory peptides generated from enzymatic hydrolysis of goat milk proteins. Biocatalysis Agric Biotechnol. 2017;11:83–8.
103. Nongonierma AB, Le Maux S, Esteveny C, FitzGerald RJ. Response surface methodology (RSM) applied to the generation of casein hydrolysates with antioxidant and dipeptidyl peptidase IV (DPP-IV) inhibitory properties. J Sci Food Agric. 2017;97:1093–101.
104. Naik L, Mann B, Bajaj R, Sangwan R, Sharma R. Process optimization for the production of bio-functional whey protein hydrolysates: adopting response surface methodology. Int J Peptide Res Therapeut. 2013;19:231–7.
105. Zhao XH, Wu D, Li TJ. Preparation and radical scavenging activity of papain-catalyzed casein plasteins. Dairy Sci Technol. 2010;90:521–35.
106. Zheng H, Shen X, Bu G, Luo Y. Effects of pH, temperature and enzyme-to-substrate ratio on the antigenicity of whey protein hydrolysates prepared by Alcalase. Int Dairy J. 2008;18:1028–33.
107. Liu X, Luo Y, Li Z. Effects of pH, temperature, enzyme-to-substrate ratio and reaction time on the antigenicity of casein hydrolysates prepared by papain. Food Agric Immunol. 2012;23:69–82.
108. Guo Y, Pan D, Tanokura M. Optimization of hydrolysis conditions for the production of the angiotensin-I converting enzyme (ACE) inhibitory peptides from whey protein using response surface methodology. Food Chem. 2009;114:328–33.
109. Tavares TG, Contreras MM, Amorim M, Martín-Álvarez PJ, Pintado ME, Recio I, et al. Optimization, by response surface methodology, of degree of hydrolysis and antioxidant and ACE-inhibitory activities of whey protein hydrolysates obtained with cardoon extract. Int Dairy J. 2011;21:926–33.
110. Vermeirssen V, Van Camp J, Devos L, Verstraete W. Release of angiotensin I converting enzyme (ACE) inhibitory activity during in vitro gastrointestinal digestion: from batch experiment to semicontinuous model. J Agric Food Chem. 2003;51:5680–7.
111. Pan D, Guo Y. Optimization of sour milk fermentation for the production of ACE-inhibitory peptides and purification of a novel peptide from whey protein hydrolysate. Int Dairy J. 2010;20:472–9.
112. Zhao X-H, Li Y-Y. An approach to improve ACE-inhibitory activity of casein hydrolysates with plastein reaction catalyzed by Alcalase. Eur Food Res Technol. 2009;229:795–805.
113. Uluko H, Li H, Cui W, Zhang S, Liu L, Chen J, et al. Response surface optimization of angiotensin converting enzyme inhibition of milk protein concentrate hydrolysates in vitro after ultrasound pretreatment. Innovative Food Sci Emerg Technol. 2013;20:133–9.
114. Quirós A, Hernández-Ledesma B, Ramos M, Martín-Álvarez PJ, Recio I. Short communication: Production of antihypertensive peptide HLPLP by enzymatic hydrolysis: Optimization by response surface methodology. J Dairy Sci. 2012;95:4280–5.
115. Nongonierma AB, Lalmahomed M, Paolella S, FitzGerald RJ. Milk protein isolate (MPI) as a source of dipeptidyl peptidase IV (DPP-IV) inhibitory peptides. Food Chem. 2017;231:202–11.
116. Nongonierma AB, Mazzocchi C, Paolella S, FitzGerald RJ. Release of dipeptidyl peptidase IV (DPP-IV) inhibitory peptides from milk protein isolate (MPI) during enzymatic hydrolysis. Food Res Int. 2017;94:79–89.
117. Asledottir T, Le TT, Petrat-Melin B, Devold TG, Larsen LB, Vegarud GE. Identification of bioactive peptides and quantification of β-casomorphin-7 from bovine β-casein A1, A2 and I after ex vivo gastrointestinal digestion. Int Dairy J. 2017;71:98–106.
118. Cunsolo V, Muccilli V, Saletti R, Foti S. Applications of mass spectrometry techniques in the investigation of milk proteome. Eur J Mass Spectrom. 2011;17:305–20.
119. Le TT, Deeth HC, Larsen LB. Proteomics of major bovine milk proteins: Novel insights. Int Dairy J. 2017;67:2–15.
120. Giacometti J, Buretić-Tomljanović A. Peptidomics as a tool for characterizing bioactive milk peptides. Food Chem. 2017;230:91–8.
121. Nongonierma AB, Gaudel C, Murray BA, Flynn S, Kelly PM, Newsholme P, et al. Insulinotropic properties of whey protein hydrolysates and impact of peptide fractionation on insulinotropic response. Int Dairy J. 2013;32:163–8.
122. Lahrichi SL, Affolter M, Zolezzi IS, Panchaud A. Food Peptidomics: Large scale analysis of small bioactive peptides - A pilot study. J Proteome. 2013;88:83–91.
123. Morifuji M, Koga J, Kawanaka K, Higuchi M. Branched-chain amino acid-containing dipeptides, identified from whey protein hydrolysates, stimulate glucose uptake rate in L6 myotubes and isolated skeletal muscles. J Nutr Sci Vitaminol. 2009;55:81–6.
124. Dallas DC, Guerrero A, Parker EA, Robinson RC, Gan J, German JB, et al. Current peptidomics: Applications, purification, identification, quantification, and functional analysis. Proteomics. 2015;15:1026–38.
125. Le Maux S, Nongonierma AB, FitzGerald RJ. Improved short peptide identification using HILIC-MS/MS: Retention time prediction model based on the impact of amino acid position in the peptide sequence. Food Chem. 2015;175:847–54.
126. Harscoat-Schiavo C, Nioi C, Ronat-Heit E, Paris C, Vanderesse R, Fournier F, et al. Hydrophilic properties as a new contribution for computer-aided identification of short peptides in complex mixtures. Anal Bioanal Chem. 2012;403:1939–49.
127. Le Maux S, Nongonierma AB, Murray B, Kelly PM, FitzGerald RJ. Identification of short peptide sequences in the nanofiltration permeate of a bioactive whey protein hydrolysate. Food Res Int. 2015;77:534–9.
128. Sagardia I, Iloro I, Elortza F, Bald C. Quantitative structure–activity relationship based screening of bioactive peptides identified in ripened cheese. Int Dairy J. 2013;33:184–90.
129. Nongonierma AB, Paolella S, Mudgil P, Maqsood S, Fitzgerald RJ. Identification of novel dipeptidyl peptidase IV (DPP-IV) inhibitory peptides in camel milk protein hydrolysates. Food Chem. 2017;Submitted.
130. Murray BA, Walsh DJ, FitzGerald RJ. Modification of the furanacryloyl-L-phenylalanylglycylglycine assay for determination of angiotensin-I-converting enzyme inhibitory activity. J Biochem Biophys Methods. 2004;59:127–37.
131. Shan L, Marti T, Sollid LM, Khosla C. Comparative biochemical analysis of three bacterial prolyl endopeptidases: Implications for coeliac sprue. Biochem J. 2004;383:311–8.
132. Lacroix IM, Li-Chan EC. Comparison of the susceptibility of porcine and human dipeptidyl-peptidase IV to inhibition by protein-derived peptides. Peptides. 2015;69:19–25.
133. Devabhaktuni A, Elias JE. Application of de novo sequencing to large-scale complex proteomics data sets. J Proteome Res. 2016;15:732–42.
134. Tagliazucchi D, Shamsia S, Helal A, Conte A. Angiotensin-converting enzyme inhibitory peptides from goats' milk released by in vitro gastro-intestinal digestion. Int Dairy J. 2017;71:6–16.
135. Zhu Y-s. Kalyankar P, FitzGerald RJ. Relative quantitation analysis of the substrate specificity of glutamyl endopeptidase with bovine α-caseins. Food Chem. 2015;167:463–7.
136. Rocha-Martin J, Fernández-Lorente G, Guisan JM. Sequential hydrolysis of commercial casein hydrolysate by immobilized trypsin and thermolysin to produce bioactive phosphopeptides. Biocatal Biotransform. 2017:1–16.
137. Cheung LK, Aluko RE, Cliff MA, Li-Chan EC. Effects of exopeptidase treatment on antihypertensive activity and taste attributes of enzymatic whey protein hydrolysates. J Funct Foods. 2015;13:262–75.
138. Barry C, O'Cuinn G, Harrington D, O'Callaghan D, Fitzgerald R. Debittering of a tryptic digest of bovine b-casein using porcine kidney general aminopeptidase and X-prolydipeptidyl aminopeptidase from Lactococcus lactis subsp. cremoris AM2. J Food Sci. 2000;65:1145–50.