Journal of Dairy Science
Volume 93, Issue 2 , Pages 437-455 , February 2010

Invited review: Physiological properties of bioactive peptides obtained from whey proteins

Received 14 July 2009 ,Accepted 18 September 2009.

References 

  1. Abubakar A, Saito T, Kitazawa H, Kawai Y, Itoh T. Structural analysis of new antihypertensive peptides derived from cheese whey protein by proteinase K digestion. J. Dairy Sci. 1998;81:3131–3138
  2. Andersen JH, Jenssen H, Gutterberg TJ. Lactoferrin and lactoferricin inhibit Herpes simplex 1 and 2 infection and exhibit synergy when combined with acyclovir. Antiviral Res. 2003;58:209–215
  3. Andersen JH, Osbakk SA, Vorland LH, Travik T, Gutterberg TJ. Lactoferrin and cyclic lactoferricin inhibit the entry of human cytomelogavirus into human fibroblasts. Antiviral Res. 2001;51:141–149
  4. Antila P, Paakkari I, Järvinen A, Mattila MJ, Laukkanen M, Pihlanto-Leppälä A, et al. Opioid peptides derived from in vitro proteolysis of bovine whey proteins. Int. Dairy J. 1991;1:215–229
  5. Barbeau J, Gauthier SF, Pouliot Y. Thermal stabilization of β-lactoblobulin by whey peptide factions. J. Agric. Food Chem. 1996;44:3939–3945
  6. Baró L, Jiménez J, Martínez-Férez A, Bouza J. Bioactive milk peptides and proteins. Ars Pharmaceutica. 2001;42:135–145
  7. Bayless KJ, David GE, Meininger GA. Isolation and biological properties of osteopontin from bovine milk. Protein Expr. Purif. 1997;9:309–314
  8. Bellamy W, Takase M, Wakabayashi H, Kawase K, Tomita M. Antibacterial spectrum of lactoferricin B, a potent bactericidal peptide derived from the N-terminal region of bovine lactoferrin. J. Appl. Bacteriol. 1992;73:472–479
  9. Bellamy W, Takase M, Yamauchi K, Wakabayashi H, Kawase K, Tomita M. Identification of the bactericidal domain of lactoferrin. Biochim. Biophys. Acta. 1992;1121:130–136
  10. Bellamy W, Wakabayashi H, Takase M, Kawase K, Shimamura S, Tomita M. Role of cell binding in the antibacterial mechanism of lactoferricin B. J. Appl. Bacteriol. 1993;75:478–484
  11. Bellamy W, Yamauchi K, Wakabayashi H, Takase M, Takakura N, Shimamura S. Antifungal properties of lactoferricin B, a peptide derived from the N-terminal region of bovine lactoferrin. Lett. Appl. Microbiol. 1994;18:230–233
  12. Berthou J, Migliore-Samour D, Lifchitz A, Delettre J, Floch F, Jolles P. Immunostimulating properties and three-dimensional structure of two tripeptides from human and cow caseins. FEBS Lett. 1987;218:55–58
  13. Beucher M, Levenez F, Yvon Y, Corring T. Effect of caseinomacropeptide (CMP) of cholecystokinin (CCK) release in rats. Reprod. Nutr. Dev. 1994;34:613–614
  14. Biziulevicius GA, Kislukhina OV, Kazlauskaite J, Zukaite V. Food-protein enzymatic hydrolysates possess both antimicrobial and immunostimulatory activities: A “cause and effect” theory of bifunctionality. FEMS Immunol. Med. Microbiol. 2006;46:131–138
  15. Bordenave S, Sannier F, Ricart G, Piot JM. Continuous hydrolysis of goat whey in an ultrafiltration reactor: Generation of alpha-lactorphin. Prep. Biochem. Biotechnol. 1999;29:189–202
  16. Boza JJ, Martínez-Augustin O, Gil A. Nutritional and antigenic characterization of an enzymatic whey protein hydrolysate. J. Agric. Food Chem. 1995;43:872–875
  17. Brody EP. Biological activities of bovine glycomacropeptide. Br. J. Nutr. 2000;84:39–46
  18. Campagna S, Mathot A-G, Fleury Y, Girardet J-M, Gaillard J-L. Antibacterial activity of lactophoricin, a synthetic 23-residue peptide derived from the sequence of bovine milk component-3 of proteose peptone. J. Dairy Sci. 2004;87:1621–1626
  19. Cassens PWJR, Visser S, Gruppen H, Voragen AGJ. β-Lactoglobulin hydrolysis. 1. Peptide composition and functional properties of hydrolysates obtained by the action of plasmin, trypsin, and Staphylococcus aureus V8 protease. J. Agric. Food Chem. 1999;47:2973–2979
  20. Chernikov MP, Nikolskaya GV, Stan EY, Shlygun GK, Vasilevskaya LS. Biological role of κ-casein glycomacropeptide. Vopr. Pitan. 1974;2:21–25
  21. Cheung HS, Wang FL, Ondetti MA, Sabo EF, Cushman DW. Binding of peptide substrates and inhibitors of angiotensin-converting enzyme. Importance of the COOH-terminal dipeptide sequence. J. Biol. Chem. 1980;225:401–407
  22. Chiba H, Yoshikawa M. Bioactive peptides derived from food proteins. Kagaku To Seibutsu. 1991;29:454–458
  23. Creusot N, Gruppen H. Enzyme-induced aggregation and gelation of proteins. Biotechnol. Adv. 2006;25:597–601
  24. Denhardt DT, Noda M. Osteopontin expression and function: Role in bone remodelling. J. Cell. Biochem. 1998;30–31:92–102
  25. di Biase AM, Pietrantoni A, Tinari A. Heparin-interacting sites of bovine lactoferrin are involved in anti-adenovirus activity. J. Med. Virol. 2003;69:495–502
  26. Didelot S, Bordenave-Juchereau S, Rosenfeld E, Piot J-M, Sannier F. Peptides released from acid goat whey by a yeast-lactobacillus association isolated from cheese microflora. J. Dairy Res. 2006;6:163–170
  27. Dionysius DA, Milne JM. Antibacterial peptides of bovine lactoferrin 494: Purification and characterization. J. Dairy Sci. 1997;80:667–674
  28. Dziuba J, Minkiewicz P. Influence of glycosylation on content of both micelle-stabilizing ability and biological properties of the C-terminal fragments of cow's κ-casein. Int. Dairy J. 1996;6:1017–1044
  29. el-Salam AMH, el-Shibiny S, Buchheim W. Characteristics and potential uses of the casein macropeptide. Int. Dairy J. 1996;6:327–341
  30. Facon MJ, Sakura BJ. Antibacterial activity of lactoferricin, lysozyme and EDTA against Salmonella enteritidis. Int. Dairy J. 1996;6:303–313
  31. FitzGerald RJ, Meisel H. Lactokinins: Whey protein-derived ACE inhibitory peptides. Nahrung/Food. 1999;43:165–167
  32. Gattegno L, Migliore-Samour D, Saffar L, Jolles P. Enhancement of phagocytic activity of human monocytic–macrophagic cells by immunostimulating peptides from human casein. Immunol. Lett. 1988;18:27–31
  33. Gauthier SF, Pouliot Y. Functional and biological properties of peptides obtained by enzymatic hydrolysis of whey proteins. J. Dairy Sci. 2003;86:78–87
  34. Gauthier SF, Vachon C, Savoie L. Enzymatic conditions of an in vitro method to study protein digestion. J. Food Sci. 1986;51:960–964
  35. Gerdes SK, Harper JW, Miller G. Applications Monograph: Cardiovascular Health Bioactive Components of Whey and Cardiovascular Health. Chicago, IL: The American Dairy Products Institute, US Dairy Export Council; 2002;
  36. Girardet JM, Linden G, Loye S, Courthaudon JL, Lorient D. Study of a mechanism of lipolysis inhibition by bovine milk proteose peptone component-3. J. Dairy Sci. 1993;76:2156–2163
  37. Glahn RP, Wortley GM, South PK, Miller DD. Inhibition of iron uptake by phytic acid tannic acid and ZnCl2: Studies using an in vitro digestion/Caco-2 cell model. J. Agric. Food Chem. 2002;50:390–395
  38. Groenink J, Walgreen-Weterings E, van’t Hof W, Veerman EC, Amerongen AVN. Cationic amphipathic peptides, derived from bovine and human lactoferrins, with antimicrobial activity against oral pathogens. FEMS Microbiol. Lett. 1999;179:217–222
  39. Grufferty MB, Fox PF. Milk alkaline proteinase. J. Dairy Res. 1988;55:609–613
  40. Gurgel PV, Carbonell RG, Swaisgood HE. Identification of peptide ligands generated by combinatorial chemistry that bind α-lactalbumin. Sep. Sci. Technol. 2001;36:2411–2431
  41. Halken S, Hansen KS, Jacobsen HP, Estmann A, Faelling AE, Hansen LG, et al. Comparison of a partially hydrolyzed infant formula with two extensively hydrolyzed formulas for allergy prevention: A prospective randomized study. Pediatr. Allergy Immunol. 2000;11:149–161
  42. Hammer J, Haheim H, Gutterberg TJ. Bovine lactoferrin is more efficient than bovine lactoferricin in inhibiting HSV-I/II replication in vitro. In:  Shimazaki K editors. Lactoferrin: Structure, Functions, and Applications. Amsterdam, the Netherlands: Elsevier Science; 2000;p. 239–243
  43. Hoek KS, Milne JM, Grieve PA, Dionysius DA, Smith R. Antibacterial activity of bovine lactoferrin-derived peptides. Antimicrob. Agents Chemother. 1997;41:54–59
  44. Ibrahim EH, Sherman G, Ward S, Fraser VJ, Kollef MH. The influence of inadequate antimicrobial treatment of bloodstream infections on patient outcomes in the ICU setting. Chest. 2000;118:146–155
  45. Ijäs H, Collin M, Finckenberg P, Pihlanto-Leppälä A, Korhonen H, Korpela P, et al. Antihypertensive opioid-like milk peptide α-lactorphin: Lack of effect on behavioural tests in mice. Int. Dairy J. 2004;14:201–205
  46. Ikeda M, Nozaki A, Sugiyama K, Tanaka T, Naganuma A, Tanaka K, et al. Characterization of antiviral activity of lactoferrin against hepatitis C virus infection in human cultured cells. Virus Res. 2000;66:51–63
  47. Iqbal G, López-Fandiño R, Jorba X, Vulfson EN. Biologically active peptides and enzymatic approaches to their production. Enzyme Microb. Technol. 1996;18:162–183
  48. Jack RW, Bierbaum G, Sahl H-G. Lantibiotics and Related Peptides. New York, NY: Springer-Verlag; 1998;
  49. Jaziri M, Migliore-Samour D, Casabianca-Pignède M-R, Keddad K, Morgat J-L, Jollès P. Specific binding sites on human phagocytic blood cells for Gly-Leu-Phe and Val-Glu-Pro-Ile-Pro-Tyr immunostimulating peptides from human milk proteins. Biochim. Biophys. Acta. 1992;1160:251–261
  50. Johnsen LB, Sùrensen ES, Petersen TE, Berglund L. Characterization of a bovine mammary gland PP3 cDNA reveals homology with mouse and rat adhesion molecule GlyCAM-1. Biochim. Biophys. Acta. 1995;1260:116–118
  51. Kang JH, Lee MK, Kim KL, Hahm K-S. Structure-biological activity relationships of 11-residue highly basic peptide segment of bovine lactoferrin. Int. J. Pept. Protein Res. 1996;48:357–363
  52. Kawasaki Y, Isoda H, Tanimoto M, Dosako S, Idota T, Ahiko K. Inhibition by lactoferrin and casein glycomacropeptide of binding of cholera toxin to its receptor. Biosci. Biotechnol. Biochem. 1992;56:195–198
  53. Kawasaki Y, Kawakami H, Tanimoto M, Dosako S, Tomizawa A, Kotake M, et al. pH-Dependent molecular weight changes of κ-casein glycomacropeptide and its preparation by ultrafiltration. Milchwissenschaft. 1993;48:191–195
  54. Kayser H, Meisel H. Stimulation of human peripheral blood lymphocytes by bioactive peptides derived from bovine milk proteins. FEBS Lett. 1996;383:18–20
  55. Kitchen BJ. Indigenous milk enzymes. In:  Fox PF editors. Developments in Dairy Chemistry. 3:London, UK: Applied Science Publishers; 1985;p. 239
  56. Korhonen H. Antibacterial and antiviral activities of whey proteins, the importance of whey and whey components in food and nutrition. In: Proc. 3rd Int. Germany: Whey Conf., Munich; 2001;p. 303–321
  57. Korhonen H, Pihlanto A. Bioactive peptides and proteins. Adv. Food Nutr. Res. 2003;47:175–176
  58. Kruger MC, Plimmer GG, Schollum LM, Haggarty N, Ram S, Palmano K. The effect of whey acidic protein fractions on bone loss in the ovariectomised rat. Br. J. Nutr. 2005;94:244–252
  59. Lam SM, Moughan PJ, Awati A, Morton HR. The influence of whey protein and glycomacropeptide on satiety in adult humans. Physiol. Behav. 2009;96:162–168
  60. Langley-Danysz P. Des hydrolysats protéiques pour développer des aliments santé. RIA Technol. Veille. 1998;581:38–40
  61. Li EW, Mine Y. Immunoenhancing effects of bovine glycomacropeptide and its derivatives on the proliferative response and phagocytic activities of human macrophage-like cells U937. J. Agric. Food Chem. 2004;52:2704–2708
  62. Lupetti A, Paulusma-Annema A, Welling MM, Senesi S, van Dissel JT, Nibbering PH. Candidacidal activities of human lactoferrin peptides derived from the N terminus. Antimicrob. Agents Chemother. 2000;44:3257–3263
  63. Madureira AR, Pereira CI, Gomes AMP, Pintado ME, Malcata FX. Bovine whey proteins—Overview on the main biological properties. Food Res. Int. 2007;40:1197–1211
  64. Maeno M, Yamamoto N, Takano T. Identification of an antihypertensive peptide from casein hydrolysate produced by a proteinase from Lactobacillus helveticus CP790. J. Dairy Sci. 1996;79:1316–1321
  65. Maes W, van Camp J, Vermeirssen V, Hemeryck M, Ketelslegers JM, Chrezenmeir J, et al. Influence of the lactokinin Ala-Leu-Pro- Met-His-Ile-Arg (ALPMHIR) on the release of endothelin-1 by endothelial cells. Regul. Pept. 2004;118:105–109
  66. Marshall SC. Casein macropeptide from whey—A new product opportunity. Food Res. Quart. 1991;51:86–89
  67. Martin-Esteban M, Garcia-Ara MC, Banque-Molas M, Boyano-Martinez MT, Martin-Munoz F, Diaz-Pena JM. Evaluation of an extensively hydrolyzed casein-whey protein formula in immediate cow's milk protein hypersensitivity. J. Pediatr. Gastroenterol. Nutr. 1998;26:398–401
  68. Maruyama S, Mitachi H, Awaya J, Kurono M, Tomizuka N, Suzuki H. Angiotensin I-converting enzyme inhibitory activity of the C-terminal hexapeptide of αS1-casein. Agric. Biol. Chem. 1987;54:2557–2561
  69. Mattsby-Balzer I, Roseanu A, Motas C, Elverfors J, Engberg I, Hanson LA. Lactoferrin or a fragment thereof inhibits the endotoxin-induced interleukin-6 response in human monocytic cells. Pediatr. Res. 1996;40:257–262
  70. McCann KB, Lee A, Wan J, Roginski H, Coventry MJ. The effect of bovine lactoferrin and lactoferricin B on the ability of feline calicivirus (a norovirus surrogate) and poliovirus to infect cell cultures. J. Appl. Microbiol. 2003;95:1026–1033
  71. Meisel H. Overview on milk protein-derived peptides. Int. Dairy J. 1998;8:363–373
  72. Meisel H, FitzGerald RJ. Biofunctional peptides from milk proteins, mineral binding and cytomodulatory effects. Curr. Pharm. Des. 2003;9:1289–1295
  73. Meisel H, Schlimme E. Bioactive peptides derived from milk proteins: Ingredients for functional foods?. Kieler Milchwirts. Forsch. 1996;48:343–357
  74. Mercier A, Gauthier SF, Fliss I. Immunomodulating effects of whey proteins and their enzymatic digests. Int. Dairy J. 2004;14:175–183
  75. Mills ENC, Alcocer MJC, Morgan MRA. Biochemical interactions of food-derived peptides. Trends Food Sci. Technol. 1992;3:64–68
  76. Minekus M, Marteau P, Havenaar R, Huis in’t Veld JHJ. A multi compartmental dynamic computer-controlled model simulating the stomach and small intestine. ATLA. 1995;23:197–209
  77. Molly K, van de Woestyne M, Verstraete W. Development of a 5-step multi-chamber reactor as a simulation of the human intestinal microbial ecosystem. Appl. Microbiol. Biotechnol. 1993;39:254–258
  78. Mullally MM, Meisel H, FitzGerald RJ. Synthetic peptides corresponding to α-LA and β-LG sequences with angiotensin-I-converting enzyme inhibitory activity. Biol. Chem. Hoppe Seyler. 1996;377:259–260
  79. Mullally MM, Meisel H, FitzGerald RJ. Angiotensin-I-converting enzyme inhibitory activities of gastric and pancreatic proteinase digests of whey proteins. Int. Dairy J. 1997;7:299–303
  80. Murakami M, Tonouchi H, Takahashi R, Kitazawa H, Kawai Y, Negishi H, et al. Structural analysis of a new anti-hypertensive peptide (β-lactosin B) isolated from a commercial whey product. J. Dairy Sci. 2004;87:1967–1974
  81. Nagaoka S, Futumura Y, Miwa K, Awano T, Yamauchi K, Kanamaru Y, et al. Identification of novel hypocholesterolemic compound derived from bovine milk beta-lactoglobulin. Biochem. Biophys. Res. Commun. 2001;281:11–17
  82. Nakamura Y, Yamamoto N, Sakai K, Takano T. Antihypertensive effect of sour milk and peptides isolated from it that are inhibitors to angiotensin I-converting enzyme. J. Dairy Sci. 1995;78:1253–1257
  83. Neeser J-R, Chambaz A, del Vedovo S, Prigent M-J, Guggenheim B. Specific and nonspecific inhibition of adhesion of oral actinomyces and streptococci to erythrocytes and polystyrene by caseinoglycopeptide derivatives. Infect. Immun. 1988;56:3201–3208
  84. Nurminen M-L, Sipola M, Kaarto H, Pihlanto-Leppälä A, Piilola K, Korpela R, et al. α-Lactorphin lowers blood pressure measured by radiotelemetry in normotensive and in spontaneously hypertensive rats. Life Sci. 2000;66:1535–1543
  85. Ohinata K, Inui A, Asakawa A, Wada K, Wada E, Yoshikawa M. Albutensin A and complement C3a decrease food intake in mice. Peptide. 2002;27:127–133
  86. Ondetti MA, Cushman DW. Enzymes of the renin-angiotensin system and their inhibitors. Annu. Rev. Biochem. 1982;51:283–308
  87. Oomen AG, Hack A, Minekus M, Zeijdner E, Cornelis C, Schoeters G, et al. Comparison of five in vitro digestion models to study the bioaccessibility of soil contaminants. Environ. Sci. Technol. 2002;36:3326–3334
  88. Ortiz-Chao P, Gomez-Ruiz JA, Rastall RA, Mills D, Cramer R, Pihlanto A, et al. Production of novel ACE inhibitory peptides from β-lactoglobulin using Protease N Amano. Int. Dairy J. 2009;19:69–76
  89. Pecquet S, Bovetto L, Maynard F, Fritsché R. Peptides obtained by tryptic hydrolysis of bovine β-lactoglobulin induce specific oral tolerance in mice. J. Allergy Clin. Immunol. 2000;105:514–521
  90. Pellegrini A, Dettling C, Thomas U, Hunziker P. Isolation and characterisation of four bactericidal domains in the bovine α-lactoglobulin. Biochim. Biophys. Acta. 2000;1526:131–140
  91. Pellegrini A, Thomas U, Bramaz N, Hunziker P, von Fellenberg R. Isolation and identification of three bactericidal domains in the bovine α-lactalbumin molecule. Biochim. Biophys. Acta. 1999;1426:439–448
  92. Perea A, Ugalde U. Continuous hydrolysis of whey proteins in a membrane recycle reactor. Enzyme Microb. Technol. 1996;18:29–34
  93. Pietrantoni A, Ammendolia MG, Tinari A, Siciliano R, Valenti P, Superti F. Bovine lactoferrin peptidic fragments involved in inhibition of echovirus 6 in vitro infection. Antivir. Res. 2006;69:98–106
  94. Pihlanto-Leppälä A, Koskinen P, Piilola K, Tupasela T, Korhonen H. Angiotensin I-converting enzyme inhibitory properties of whey protein digests: Concentration and characterization of active peptides. J. Dairy Res. 2000;67:53–64
  95. Pihlanto-Leppälä A, Paakkari I, Rinta-Koski M, Antila P. Bioactive peptide derived from in vitro proteolysis of bovine β-lactoglobulin and its effect on smooth muscle. J. Dairy Res. 1997;64:149–155
  96. Pihlanto-Leppälä A, Rokka T, Korhonen H. Angiotensin I-converting enzyme inhibitory peptides from bovine milk proteins. Int. Dairy J. 1998;8:325–331
  97. Pins JJ, Keenan JM. Effects of whey peptides on cardiovascular disease risk factors. J. Clin. Hypertens. 2006;8:775–782
  98. Potter S. Overview of proposed mechanisms for the hypocholesterolemic effect of soy. J. Nutr. 1995;125:606–611
  99. Prioult G, Pecquet S, Fliss I. Stimulation of interleukin-10 production by acidic beta-lactoglobulin-derived peptides hydrolyzed with Lactobacillus paracasei NCC2461 peptidases. Clin. Diagn. Lab. Immunol. 2004;11:266–271
  100. Recio I, Visser S. Two ion-exchange chromatographic methods for the isolation of antibacterial peptides from lactoferrin: In situ enzymatic hydrolysis on an ion-exchange membrane. J Chromatogr. 1999;831:191–201
  101. I. R., J. Cornish, N. W. Haggarty, and K. P. Palmano. 2004. Bone health compositions derived from milk. US patent US2004052860. New Zealand Dairy Board, assignee.
  102. Roufik S, Gauthier SF, Sylvie LT. Physicochemical characterization and in vitro digestibility of β-lactoglobulin/β-Lg f142–148 complexes. Int. Dairy J. 2007;7:471–480
  103. Roufik S, Gauthier SF, Turgeon SL. In vitro digestibility of bioactive peptides derived from bovine β-lactoglobulin. Int. Dairy J. 2006;16:294–302
  104. Saint-Sauveur D, Gauthier SF, Boutin Y, Montoni A, Fliss I. Effect of feeding whey peptide fractions on the immune response in healthy and Escherichia coli infected mice. Int. Dairy J. 2009;19:537–544
  105. Saito T, Nakamura T, Kitazawa H, Kawai Y, Itoh T. Isolation and structural analysis of antihypertensive peptides that exist naturally in Gouda cheese. J. Dairy Sci. 2000;83:1434–1440
  106. Samuelsen Ø, Haukland HH, Ulvatne H, Vorland LH. Anti-complement effects of lactoferrin-derived peptides. FEMS Immunol. Med. Microbiol. 2004;41:141–148
  107. Schmidt RH, Packardm VS, Morris HA. Effects of processing on whey protein functionality. J. Dairy Sci. 1984;67:2723–2733
  108. Schupbach P, Neeser JR, Golliard M, Rouvet M, Guggenheim B. Incorporation of caseinoglycomacropeptide and caseinophosphopeptide into the salivary pellicle inhibits adherence of mutant streptococci. J. Dent. Res. 1996;75:1779–1788
  109. Scollard PG, Beresford TP, Murphy PM, Kelly AL. Barostability of milk plasmin activity. Lait. 2000;80:609–619
  110. Shah NP. Effects of milk-derived bioactives: An overview. Br. J. Nutr. 2000;84(Suppl. 1):S3–S10
  111. Shimazaki K, Tazume T, Uji K, Tanaka M, Kumura H, Mikawa K, et al. Properties of a heparin-binding peptide derived from bovine lactoferrin. J. Dairy Sci. 1998;81:2841–2849
  112. Shin K, Yamauchi K, Teraguchi S, Hayasawa H, Tomita M, Otsuka Y, et al. Antibacterial activity of bovine lactoferrin and its peptides against enterohaemorrhagic Escherichia coli O157 7. Lett. Appl. Microbiol. 1998;26:407–411
  113. Siciliano R, Rega B, Marchetti M, Seganti L, Antonini G, Valenti P. Bovine lactoferrin peptidic fragments involved in inhibition of herpes simplex virus type 1 infection. Biochem. Biophys. Res. Commun. 1999;264:19–23
  114. Silva SV, Malcata FX. Caseins as source of bioactive peptides. Int. Dairy J. 2004;15:1–15
  115. Sipola M, Finckenberg P, Korpela R, Vapaatalo H, Nurminen M-L. Effect of long-term intake of milk products on blood pressure in hypertensive rats. J. Dairy Res. 2002;69:103–111
  116. Smacchi E, Gobbetti M. Bioactive peptides in dairy products, synthesis and interaction with proteolytic enzymes. Food Microbiol. 2000;17:129–141
  117. Smithers GW, Ballard JB, Copeland AD, Kirthi JA, Dionysius DA, Francis GL, et al. Symposium: Advances in dairy foods processing and engineering new opportunities from the isolation and utilization of whey proteins. J. Dairy Sci. 1996;79:1454–1459
  118. Sorensen ES, Petersen T. Purification and characterization of three proteins from the proteose peptone fraction of bovine milk. J. Dairy Res. 1993;60:189–197
  119. Sorensen ES, Rasmussen LK, Moller L, Petersen TE. The localization and multimeric nature of component PP3 in bovine milk: Purification and characterization of PP3 from caprine and ovine milks. J. Dairy Sci. 1997;80:3176–3181
  120. Takahashi M, Moriguchi SM, Suganuma T, Shiota H, Takenaka A, Tani Y, et al. Albutensin A an ileum-contracting peptide derived from serum albumin acts through both receptors for complements C3a and C5a. Lett. Pept. Sci. 1998;5:29–35
  121. Tani F, Shiota A, Chiba H, Yoshikawa M. Serophin an opioid peptide derived from bovine serum albumin. In:  Brantl V editors. β-Casomorphins and Related Peptides: Recent Developments. Weinheim, Germany: VCH-Verlag; 1993;p. 49–53
  122. Tomé D, Ledoux N. Nutritional and physiological role of milk protein components. Dairy Foods in Health Bulletin of the International Dairy Federation. 336. Brussels, Belgium: International Dairy Federation; 1998;11–16
  123. Tomita M, Bellamy W, Takase M, Yamauchi K, Wakabayashi H, Kawase K. Potent antibacterial peptides generated by pepsin digestion of bovine lactoferrin. J. Dairy Sci. 1992;74:4137–4142
  124. Tyler-McMahon BM, Bolles M, Richelson E. Neurotensin: Peptide for the next millennium. Regul. Pept. 2000;93:125–126
  125. van der Kraan MIA, Groenink J, Nazmi K, Veerman ECI, Bolscher JGJ, Amerongen AVN. Lactoferrampin: A novel antimicrobial peptide in the N1-domain of bovine lactoferrin. Peptides. 2004;25:177–183
  126. van der Kraan MIA, Nazmi K, Teeken A, Groenink J, van’t Hoff W, Veerman ECI. Lactoferrampin an antimicrobial peptide of bovine lactoferrin exhibits its candidacidal activity by a cluster of positively charged residues at the C-terminus in combination with a helix facilitating N-terminal part. J. Biol. Chem. 2005;386:137–142
  127. Vermeirssen V, Deplacke B, Tappenden KA, van Camp J, Gaskins HR, Verstraete W. Intestinal transport of the lactokinin Ala-Leu-Pro-Met-His-Ile-Arg through a Caco-2 Bbe monolayer. J. Pept. Sci. 2002;8:95–100
  128. Viejo-Díaz M, Andrés MT, Fierro JF. Different anti-Candida activities of two lactoferrin-derived peptides Lfpep and kaliocin-1. Antimicrob. Agents Chemother. 2005;49:2583–2588
  129. Vogel HJ, Shibli DJ, Jing W, Lohmeiher-Vogel EM, Epand RF, Epand RM. Towards a structure-function analysis of bovine lactoferricin and related tryptophan- and arginine-containing peptides. Biochem. Cell Biol. 2002;80:49–63
  130. Vorland LH, Ulvatne H, Rekdal O, Svendsen JS. Initial binding sites of antimicrobial peptides in Staphylococcus aureus and Escherichia coli. Scand. J. Infect. Dis. 1999;31:467–473
  131. Wakabayashi H, Abe S, Okutomi T, Tansho S, Kawase K, Yamaguchi H. Cooperative anti-Candida effects of lactoferrin or its peptides in combination with azole antifungal agents. Microbiol. Immunol. 1996;40:821–825
  132. Wakabayashi H, Matsumoto H, Hashimoto K, Teraguchi S, Takase M, Hayasawa H. N-Acylated and d-enantiomer derivatives of a nonamer core peptide of lactoferricin B showing improved antimicrobial activity. Antimicrob. Agents Chemother. 1999;43:1267–1269
  133. Wakabayashi H, Takase M, Tomita M. Lactoferricin derived from milk protein lactoferrin. Curr. Pharm. Des. 2003;9:1277–1287
  134. Walsh DJ, Bernard H, Murray BA, MacDonald J, Pentzien A-K, Wright GA, et al. In vitro generation and stability of the lactokinin β-lactoglobulin fragment (142–148). J. Dairy Sci. 2004;87:3845–3857
  135. Wong KF, Middleton N, Montgomery M, Dey M, Carr RI. Immunostimulation of murine spleen cells by materials associated with bovine milk protein fractions. J. Dairy Sci. 1998;81:1825–1832
  136. Yamamoto N, Maeno M, Takano T. Purification and characterization of an antihypertensive peptide from a yogurt-like product fermented by Lactobacillus helveticus CPN4. J. Dairy Sci. 1999;82:1388–1393
  137. Yamauchi K. Biologically functional proteins of milk and peptides derived from milk proteins. Bull. Int. Dairy Fed. 1992;272:51–58
  138. Yamauchi K, Tomita M, Giehl TJ, Ellison RT. Antibacterial activity of lactoferrin and a pepsin-derived lactoferrin peptide fragment. Infect. Immun. 1993;61:719–728
  139. Yamauchi R, Ohinata K, Yoshikawa M. β-Lactotensin and neurotensin rapidly reduce serum cholesterol via NT2 receptor. Peptides. 2003;24:1955–1961
  140. Yamauchi R, Usui H, Yunden J, Takenaka Y, Tani F, Yoshikawa M. Characterization of β-lactotensin a bioactive peptide derived from bovine β-lactoglobulin as a neurotensin agonist. Biosci. Biotechnol. Biochem. 2003;67:940–943
  141. Yvon M, Beucher S, Guilloteau P, le Huerou-Luron I, Corring T. Effects of caseinomacropeptide (CMP) on digestion regulation. Reprod. Nutr. Dev. 1994;34:527–537
  142. Yvon M, Beucher S, Scanff P, Thirouin S, Pelissier JP. In vitro simulation of gastric digestion of milk proteins: Comparison between in vitro and in vivo data. J. Agric. Food Chem. 1992;40:239–244
  143. Zhang X, Beynen AC. Influence of dietary fish proteins on plasma and liver cholesterol concentrations in rats. Br. J. Nutr. 1993;69:767–777

PII: S0022-0302(10)71487-9

doi: 10.3168/jds.2009-2566

Journal of Dairy Science
Volume 93, Issue 2 , Pages 437-455 , February 2010