Milk Protein Hydrolysates and Bioactive Peptides

  • R. J. Fitzgerald
  • H. Meisel

Abstract

The basic function of milk proteins has long been thought to be that of providing nitrogen and essential amino acids for young mammals (Hambræus, 1992). In addition, intact milk proteins have a range of biological activities, e.g., itnmunoglobulins have an immunoprotective effect, lactoferrin displays antibacterial activity while low concentrations of growth factors and hormones, mainly present in colostrum, appear to play a significant role in post-natal development (Schanbacher et al., 1998). Milk proteins also contain a large range of bioactive peptide sequences which are encrypted within their primary structures (Table 14.1, Meisel, 1998). These include opioid agonist and antagonist peptides, potential hypotensive peptides which inhibit angiotensin-I-converting enzyme (ACE), mineral binding, immunomodulatory, antibacterial and antithrombotic peptides (FitzGerald, 1998; Meisel, 1998; Schanbacher et al., 1998; Takano, 1998; Tomé and Debabbi, 1998; Meisel and Bockelmann, 1999).

Keywords

Placebo Hydrolysis Fermentation Morphine Proline 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

REFERENCES

  1. Abubakar, A., Saito, T., Kitazawa, H., Kawai, Y. and Itoh, T. (1998) Structural analysis of new antihypertensive peptides derived from cheese whey protein by proteinase K digestion. J. Dairy Sci., 81, 3131–8.Google Scholar
  2. Adamson, N.J. and Reynolds, E.G. (1995) Characterisation of tryptic casein phosphopeptides prepared under industrially relevant conditions. Biotech. Bioeng., 45, 196–204.Google Scholar
  3. Antila, P., Paakkari, I., Järvinen, A., Mattila, M.J., Laukkanen, M., Pihlanto-Leppälä, A., Mänstsälä, P. and Hellman, J. (1991) Opioid peptides derived from in-vitro proteolysis of bovine whey proteins. Int. Dairy J., 1, 215–29.Google Scholar
  4. Bellamy, W., Takase, M., Yamauchi, K., Kawase, K., Shimamura, S. and Tomita, M. (1992) Identification of the bactericidal domain of lactoferrin. Biochim. Biophys. Acta, 1121, 130–6.Google Scholar
  5. Bellamy, W., Wakabayashi, H., Takase, M., Kawase, K., Shimamura, S. and Tomota, M. (1993) Role of cell-binding in the antibacterial mechanism of lactoferricin B. J. Appl. Bacteriol., 75, 478–84.Google Scholar
  6. Berrocal, R., Chanton, S., Juillerat, M.A., Pavillard, B., Scherz, J.-C. and Jost, R. (1989) Tryptic phosphopeptides from whole casein: II. Physicochemical properties related to the solubilisation of calcium. J. Dairy Res., 56, 335–41.Google Scholar
  7. Bouchier, P., FitzGerald, R.J. and O’Cuinn, G. (1999) Hydrolysis of αs1-and β-casein-derived peptides with a broad specificity aminopeptidase and with proline specific aminopeptidases from Lactococcus lactis spp. cremoris AM2. FEBS Lett., 445, 321–4.Google Scholar
  8. Bouhallab, S., Mollé, D. and Léonil, J. (1992) Tryptic hydrolysis of caseinomacro-peptide in a membrane reactor, preparation of bioactive peptides. Biotechnol. Lett., 14, 805–10.Google Scholar
  9. Brandsch, M., Brust, P., Neubert, K. and Ermisch, A. (1994) β-Casomorphins-chemical signals of intestinal transport systems, in, β-Casomorphins and Related Peptides: Recent Developments, (V. Brantl and H. Teschemacher eds.) VCH, Weinheim, pp. 207–19.Google Scholar
  10. Brantl, V., Teschemacher, H., Bläsig, J., Henschen, A. and Lottspeich, F. (1981) Opioid activities of β-casomorphins. Life Sci., 28, 1903–9.Google Scholar
  11. Brulé, G., Roger, L., Fauquant, J. and Piot, M. (1989) Casein phosphopeptide composition. US Patent, 4,816.398.Google Scholar
  12. Bruneval, P., Hinglais, N. and Alhenc-Gelas, F. (1986) Angiotensin I converting enzyme in human intestine and kidney. Ultrastructural immunohistochemical localization. Histochem., 86, 73–80.Google Scholar
  13. Carnie, J., Minter, S., Oliver, S., Perra, F. and Metzlaff, M. (1989) Nutritional compositions containing β-casomorphins. UK Patent Application GB 2214810 A.Google Scholar
  14. Chabance, B., Joliès, P., Izquierdo, C., Mazoyer, E., Francoual, C., Drouet, L. and Fiat, A.-M. (1995) Characterisation of an antithrombotic peptide from κ-casein in newborn plasma after milk ingestion. Br. J. Nutr., 73, 583–90.Google Scholar
  15. Chabance, B., Marteau, P., Rambaud, J.C., Migliore-Samour, D., Boynard, M., Perrotin, P., Guillet, R., Joliès, P. and Fiat, A.-M. (1998) Casein peptide release and passage to the blood in humans during digestion of milk or yoghurt. Biochimie, 80, 155–65.Google Scholar
  16. Chang, K.J., Killian, A., Hazum, E. and Cuatrecasas, P. (1981) Morphiceptin: A potent and specific agonist for morphine (μ) receptors. Science, 212, 75–7.Google Scholar
  17. Chang, K.J., Fu Su, Y., Brent, D.A. and Chang, J.-K. (1985) Isolation of a specific μ-opiate receptor peptide, morphiceptin, from an enzymatic digest of milk proteins. J. Biol. Chem., 260, 9706–12.Google Scholar
  18. Cheung, H.-S., Feng-Lai, W., Ondetti, M.A., Sabo, E.F. and Cushman, D.W. (1980) Binding of peptide substrates and inhibitors of angiotensin-converting-enyzme. J. Biol. Chem., 255, 401–7.Google Scholar
  19. Chiba, H. and Yoshikawa, M. (1986) Biologically functional peptides from food proteins: New opioid peptides from milk proteins, in Protein Tailoring for Food and Medical Uses, (R.E. Feeney and J.R. Whitaker eds.) Marcel Dekker Inc., New York, pp. 123–53.Google Scholar
  20. Chiba, H., Tani, F. and Yoshikawa, M. (1989) Opioid antagonist peptides derived from κ-casein. J. Dairy Res., 56, 363–6.Google Scholar
  21. Chiba, H. and Yoshikawa, M. (1991) Bioactive peptides derived from food proteins. Kagaku to Seibutsu., 29, 454–8.Google Scholar
  22. Coste, M., Rochet, V., Léonil, J., Mollé, D., Bouhallab, B. and Tomé, D. (1992) Identification of the C-terminal peptides of bovine β-casein that enhance proliferation of rat lymphocytes. Immunol. Lett., 33, 41–6.Google Scholar
  23. Daniel, H., Vohwinkel, M. and Rehner, G. (1990a) Effect of casein and β-casomorphins on gastrointestinal motility in rats. J. Nutr., 120, 252–7.Google Scholar
  24. Daniel, H., Wessendorf, A., Vohwinkel, M. and Brantl, V. (1990b) Effect of D-Ala2.4Tyr5-β-casomorphin-5-amide on gastrointestinal functions, in β-Casomorphins and Related Peptides, (F. Nyberg and V. Brantl eds.) Fyris-Tryck AB, Uppsala, pp. 95–104.Google Scholar
  25. Dionysius, D.A. and Milne, J.M. (1998) Antibacterial peptides of bovine lactoferrin: purification and characterizaton. J. Dairy Sci., 80, 667–74.Google Scholar
  26. Elitsur, Y. and Luk, G.D. (1991) β-Casomorphin (BCM) and human colonic lamina propria lymphocyte proliferation. Clin. Exper. Immunol., 85, 493–97.Google Scholar
  27. Ellegård, K.H., Gammelgård-Larsen, C., Sørensen, E.S. and Fedosov, S. (1999) Process scale Chromatographic isolation, characterisation and identification of tryptic bioactive casein phosphopeptides. Int. Dairy. J., 9, 639–52.Google Scholar
  28. Fiat, A.-M. and Joliès, P. (1989) Caseins of various origins and biologically active casein peptides and oligosaccharides: structural and physiological aspects. Mol. Cell. Biochem., 87, 5–30.Google Scholar
  29. Fiat, A.-M., Migliore-Samour, D., Joliès, P., Drouet, L., Collier, C. and Caen, J. (1993) Biologically active peptides from milk proteins with emphasis on two examples concerning antithrombotic and immunomodulating activities. J. Dairy Res., 76, 301–10.Google Scholar
  30. FitzGerald, R.J. (1998) Potential uses of caseinophosphopeptides. Int. Dairy J., 8, 451–7.Google Scholar
  31. FitzGerald, R.J. and Meisel, H. (1999) Lactokinins: Whey protein-derived ACE inhibitory peptides. Nahrung., 43, 165–7.Google Scholar
  32. FitzGerald, R.J. and Meisel, H. (2000) Milk protein — derived peptide inhibitors of angiotensin-I-converting enzyme. Br. J. Nutr., 84(SI), 33–7.Google Scholar
  33. FitzGerald, R.J., Smyth, M., McDonagh, D. and Slattery H. (1996) Applications of milk protein hydrolysates, in Proceedings 3rd Food Ingredients Symposium, (M.K. Keogh ed.) Teagasc, Dublin, pp. 76–86.Google Scholar
  34. Goepfert, A. and Meisel, H. (1996) Semi-preparative isolation of phosphopeptides derived from casein and dephosphorylation of casein phosphopeptides. Nahrung., 40, 245–8.Google Scholar
  35. Hadden, J.W. (1991) Immunotherapy of human immunodeficiency virus infection. Trends Pharm. Sci., 12, 107–11.Google Scholar
  36. Haileselassie, S.S., Lee, B.H. and Gibbs B.F. (1999) Purification and identification of potentially bioactive peptides from enzyme-modified cheese. J. Dairy Sci., 82, 1612–7.Google Scholar
  37. Hambræus, L. (1992) Nutritional aspects of milk proteins, in Advanced Dairy Chemistry-1. Proteins, 2nd edn., (P.F. Fox ed.) Elsevier Applied Science, London, pp. 57–90.Google Scholar
  38. Hamel, U., Kielwein, G. and Teschemacher, H. (1985) β-Casomorphin immunoreactive materials in cow’s milk incubated with various bacterial species. J. Dairy Res., 52, 139–48.Google Scholar
  39. Hansen, M., Sandstöm, B., Jensen, M. and Sörensen, S.S. (1997) Casein phosphopeptides improve zinc and calcium absorption from rice-based but not from whole grain infant cereal. J. Pediatr. Gastroenterol. Nutr., 24, 56–62.Google Scholar
  40. Hata, Y., Yamamoto, M., Ohni, M., Nakajima, K., Nakamura, Y. and Takano, T. (1996) A placebo-controlled study of the effect of sour milk on blood pressure in hypertensive subjects. Am. J. Clin, Nutr., 64, 767–71.Google Scholar
  41. Hata, I., Higashiyama, S. and Otani, H. (1998) Identification of a phosphopeptide in bovine αs1-casein digest as a factor influencing proliferation and immunoglobulin production in lymphocyte cultures. J. Dairy Res., 65, 569–79.Google Scholar
  42. Hata, I., Ueda, J. and Otani, H. (1999) Immunostimulatory action of commercially available casein phosphopeptide preparations, CPP-III, in cell cultures. Milchwisswenchaft, 1, 3–7.Google Scholar
  43. Höllt, V. (1983) Multiple endogenous opioid peptides. Trends Neurosci., 6, 24–6.Google Scholar
  44. Johnston, C.I. (1992) Renin-angiotensin system: a dual tissue and hormonal system for cardiovascular control. J. Hyperten., 10, S13–26.Google Scholar
  45. Joliès, P., Parker, F., Floc’h, F., Migliore, D., Alliel, P., Zerial, A. and Werner, G.G. (1981) Immunostimulating substances from human casein. J. Pharmacol., 3, 363–9.Google Scholar
  46. Joliès, P., Lévy-Toledano, S., Fiat, A.-M., Soria, C., Gillessen, D., Thomaidis, A., Dunn, F.W. and Caen, J.B. (1986) Analogy between fibrinogen and casein. Eur. J. Biochem., 158, 379–84.Google Scholar
  47. Juillard, V., Laan, H., Kunji, E.R.S., Jeronimus-Stratingh, C.M., Bruins, A.P. and Konings, W.N. (1995) The extracellular Pi-type proteinase of Lactococcus lactis hydrolyzes β-casein into more than one hundred different oligopeptides. J. Bacterial., 177, 3472–8.Google Scholar
  48. Juillerat, M.A., Baechler, R., Berrocal, R., Chanton, S., Scherz, J.-C. and Jost, R. (1989) Tryptic phosphopeptides from whole casein I; Preparation and analysis by FPLC. J. Dairy Res., 56, 603–11.Google Scholar
  49. Kampa, M., Loukas, S., Hatzoglou, A., Daminaki, A., Martin, P.M. and Castanas, E. (1997) Opioid alkaloids and casomorphin peptides decrease the proliferation of prostatic cancer cell lines (LNCaP, PC3 and DU145) through partial interaction with opioid receptors. Eur. J. Pharmacol., 335, 255–65.Google Scholar
  50. Kang, J.H., Lee, M.K., Kim, K.L. and Hahm, K.S. (1996) Structure biological activity relationship of 11-residue highly basic peptide segment of bovine lactoferrin. Int. J. Pep. Prot. Res., 48, 357–63.Google Scholar
  51. Karaki, H., Doi, K., Sugano, S., Uchiya, H., Sugai, R., Murakami, U. and Takemoto, S. (1990) Antihypertensive effect of tryptic hydrolysate of milk casein in spontaneously hypertensive rats. Comp. Biochem. Physiol., 96, 367–71.Google Scholar
  52. Kasai, T., Honda, T. and Kiriyama, S. (1992) Caseinophosphopeptides (CPP) in faeces of rats fed a casein diet. Biosci. Biotechnol. Biochem., 56, 1150–1.Google Scholar
  53. Kayser, H. and Meisel, H. (1996) Stimulation of human peripheral blood lymphocytes by bioactive peptides derived from bovine milk proteins. FEBS Lett., 383, 18–20.Google Scholar
  54. Kitts, D.D. and Yuan, Y.V. (1992) Caseinophosphopeptides and calcium bioavailability. Trends Food Sci. Technol., 3, 31–5.Google Scholar
  55. Koide, H., Ito, K., Miyamoto, M. and Nishino, H. (1980) Effect of long-term blockade of angiotensin-converting enzyme with captopril (SQ 14 22S) on haemodynamics and circulating blood volume in SHR. Hypertension, 2, 229–303.Google Scholar
  56. Koide, K., Itoyama, K., Fukushima, T., Miyazawa, F. and Kuwata, T. (1991) Method for separation and concentration of phosphopeptides. European Patent Application EP, 0 443 718 A2.Google Scholar
  57. Kunst, A. (1990) Process to isolate phosphopeptides. European Patent Application EP 0 476 199 Al.Google Scholar
  58. Lahov, E. and Regelson, W. (1996) Antibacterial and immunostimulating caseinderived substances from milk: casesidin, isracidin peptides. Food Chem. Toxicol., 34, 131–45.Google Scholar
  59. Lihme, A.O.F., Aagesen, M.I., Gamalgard-Larsen, C. and Ellegard, K.H. (1994) Method for isolating biomolecules by ion exchange. World Patent WO 94/06822.Google Scholar
  60. Loukas, S., Varoucha, D., Zioudrou, C., Streaty, R.A. and Klee, W.A. (1983) Opioid activities and structures of α-casein-dervied exorphins. Biochem., 22, 4567–73.Google Scholar
  61. Maeno, M., Yamamoto, N. and Takano T. (1996) Identification of antihypertensive peptides from casein hydrolysate produced by a proteinase from Lactobacillus helveticus CP790. J. Dairy Sci., 73, 1316–21.Google Scholar
  62. Manson, W. and Annan, W.D. (1971) The structure of a phosphopeptide derived from β-casein. Arch. Biochem. Biophys., 145, 16–26.Google Scholar
  63. Maruyama, S. and Suzuki, H. (1982) A peptide inhibitor of angiotensin-I-converting enzyme in the tryptic hydrolysate of casein. Agric. Biol. Chem., 46, 1393–94.Google Scholar
  64. Maruyama, S., Nakagomi, K., Tomizuka, N. and Suzuki, H. (1985) Angiotensin I-converting enzyme inhibitor derived from an enzymatic hydrolysate of casein. II. Isolation and bradykinin-potentiating activity on the uterus and the ileum of rats. Agric. Biol. Chem., 49, 1405–9.Google Scholar
  65. Maruyama, S., Mitachi, H., Tanaka, H., Tomizuka, N. and Suzuki, H. (1987a) Studies on the active site and antihypertensive activity of angiotensin I-converting enzyme inhibitors derived from casern. Agric. Biol. Chem., 51, 1581–6.Google Scholar
  66. Maruyama S., Mitachi, H., Awaya, J., Kurono, M., Tomizika, N. and Suzuki H. (1987b) Angiotensin I converting enzyme inhibitory activity of the C-terminal hexapeptide of αs1-casein. Agric. Biol. Chem., 51, 2557–61.Google Scholar
  67. McDonagh, D. and FitzGerald, R.J. (1998) Production of caseinophosphopeptides (CPPs) from sodium caseinate using a range of commercial protease preparations. Int. Dairy J., 8, 39–45.Google Scholar
  68. Meisel, H. (1986) Chemical characterisation and opioid activity of an exorphin isolated from in vivo digests of casein. FEBS Lett., 196, 223–7.Google Scholar
  69. Meisel, H. (1993) Casokinins as inhibitors of angiotensin-I-converting enzyme, in New Perspectives in Infant Nutrition, (G. Sawatski and B. Renner eds.) Thieme, Stuttgart, pp. 153–9.Google Scholar
  70. Meisel, H. and Frister, H. (1988) Chemical characterization of a caseinophosphopeptide isolated from in vivo digests of a casein diet. Biol. Chem. Hoppe-Seyler, 369, 1275–9.Google Scholar
  71. Meisel, H. and Frister, H. (1989) Chemical characterization of bioactive peptides from in vivo digests of casein. J. Dairy Res., 56, 343–9.Google Scholar
  72. Meisel, H. (1994) Antibodies from egg yolk of immunised hens against a bioactive caseinophosphopeptide (β-casokinin-10). Biol. Chem. Hoppe-Seyler, 375, 401–5.Google Scholar
  73. Meisel, H. and Schlimme, E. (1994) Inhibitors of angiotensin-converting-enzyme derived from bovine casein (casokinins), in, β-Casomorphins and Related Peptides: Recent developments, (V. Brantl and H. Teschemacher eds.) VCH, Weinheim, pp. 27–33.Google Scholar
  74. Meisel, H. (1997) Biochemical properties of bioactive peptides derived from milk proteins: potential nutraceuticals for food and pharmacological applications. Liv. Prod. Sci., 50, 125–38.Google Scholar
  75. Meisel, H., Goepfert, A. and Gönther, S. (1997) Occurrence of ACE inhibitory peptides in milk products. Milchwissenschaft, 52, 307–11.Google Scholar
  76. Meisel, H. (1998) Overview of milk protein-derived peptides. Int. Dairy J., 8, 363–73.Google Scholar
  77. Meisel, H. and Bockelmann, W. (1999) Bioactive peptides encrypted in milk proteins: proteolytic activation and trophofunctional properties. Ant. van Leeuwen., 76, 207–15.Google Scholar
  78. Meisel, H. and FitzGerald, R.J. (2000) Opioid peptides encrypted in intact milk protein sequences. Br. J. Nutr., 84(S1), 27–31.Google Scholar
  79. Meisel, H., Bernard, H., Fairweather-Tait, S., FitzGerald, R.J., Hartmann, R., Lane, C.N., McDonagh, D., Teucher, B. and Wal, J.-M. (2001) Nutraceutical and functional food ingredients for food and pharmaceutical applications. Br. J. Nutr. 85, 635 (1 page).Google Scholar
  80. Migliore-Samour, D., FlocTi, F. and Joliès, P. (1989) Biologically active casein peptides implicated in immunomodulation. J. Dairy Res., 56, 357–62.Google Scholar
  81. Muehlenkamp, M.R. and Warthesen, J.J. (1996) β-Casomorphins: analysis in cheese and susceptibility to proteolytic enzymes from Lactococcus lactis ssp. cremoris. J. Dairy Sci., 79, 20–6.Google Scholar
  82. Mullally, M.M., O’Callaghan, D.M., FitzGerald, R.J., Donnelly, W.J. and Dalton, J.P. (1994) Proteolytic and peptidolytic activities in commercial pancreatic proteinase preparations and their relationship to some whey protein hydrolysate characterisitics. J. Agric. Food Chem., 42, 2973–81.Google Scholar
  83. Mullally, M.M., Meisel, H. and FitzGerald, R.J. (1996) Synthetic peptides corresponding to α-lactalbumin and β-lactoglobulin sequences with angiotensin-I-converting enzyme inhibitory activity. Biol. Chem. Hoppe-Seyler, 377, 259–60.Google Scholar
  84. Mullally, M.M., Meisel, H. and FitzGerald, R.J. (1997a) Identification of a novel angiotensin-I-converting enzyme inhibitory peptide corresponding to a tryptic digest of bovine β-lactoglobulin. FEBS Lett., 402, 99–101.Google Scholar
  85. Mullally, M.M., Meisel, H. and FitzGerald, R.J. (1997b) Angiotensin-I-converting enzyme inhibitory activities of gastric and pancreatic proteinase digests of whey proteins. Int. Dairy J., 7, 299–303.Google Scholar
  86. Naito, H., Kawakami, A. and Inamura, T. (1972) In vivo formation of phosphopeptide with calcium-binding property in the small intestinal tract of the rat fed on casein. Agric. Biol. Chem., 36, 409–15.Google Scholar
  87. Nakamura, Y., Yamamoto, N., Sakai, K., Okubo, A., Yamazaki, S. and Takano, T. (1995) Purification and characterization of angiotensin I-converting enzyme inhibitors from a sour milk. J. Dairy Sci., 78, 777–83.Google Scholar
  88. Ondetti, M.A. and Cushman, D.W. (1982) Enzymes of the renin-angiotensin system and their inhibitors. Ann. Rev. Biochem., 51, 283–308.Google Scholar
  89. Park, O., Swaisgood, H.E. and Alien, J.C. (1998) Calcium binding of phosphopeptides derived from hydrolysis of αs1-casein or β-casein using immobilised enzymes. J. Dairy Sci., 81, 2850–57.Google Scholar
  90. Pihlanto-Leppällä, A., Antila, P., Mäntsälä, P. and Hellman, J. (1994) Opioid peptides produced by in vitro proteolysis of bovine caseins. Int. Dairy J., 4, 291–301.Google Scholar
  91. Pihlanto-Leppälä, A., Koskinen, P., Paakkari, I., Tupasela, T. and Korhonen, H. (1996) Opioid whey protein peptides obtained by membrane filtration, Bulletin 311, International Dairy Federation, Brussels, pp. 36–8.Google Scholar
  92. Pihlanto-Leppälä, A., Rokka, T. and Korhonen, H. (1998) Angiotensin I converting enzyme inhibitory peptides derived from bovine milk proteins. Int. Dairy J., 8, 325–31.Google Scholar
  93. Pihlanto-Leppälä, A., Marnila, P., Rokka, T., Korhonen, H. and Karp, M. (1999) The effect of α-lactalbumin and β-lactoglobulin hydrolysates on the metabolic activity of Escherichia coli JM103. J. Appl. Microbiol., 87, 540–5.Google Scholar
  94. Recio, I. and Visser, S. (1999) Two ion-exchange methods for the isolation of antibacterial peptides from lactoferrin — in situ enzymatic hydrolysis on an ionexchange membrane. J. Chromatogr., 831, 191–201.Google Scholar
  95. Reeves, R.E. and Latour, N.G. (1958) Calcium phosphate sequestering phosphopeptide from casein. Science, 128, 472. (1 page)Google Scholar
  96. Reynolds, E. (1987) Phosphopeptides. PCT Int. Patent Application WO 87/07615 Al.Google Scholar
  97. Reynolds, E.C. (1992) Production of phosphopeptides from casein. World Patent Application WO 92/18526.Google Scholar
  98. Reynolds, E.C. (1994) Anticariogenic Casein Phosphopeptides. Proc. 24th Int. Dairy Congr., Brief Communications Melbourne, Australia, p. 24 (abstr).Google Scholar
  99. Righetti, P.G., Nembri, F., Bossi, A. and Mortarino, M. (1997) Continuous enzymatic hydrolysis of beta-casein and isoelectric collection of some of the biologically active peptides in an electric field. Biotechnol. Prog., 13, 258–64.Google Scholar
  100. Rokka, T., Syvaoja, E.-L., Tuominen, J. and Korhonen, H. (1997) Release of bioactive peptides by enzymatic proteolysis of Lactobacillus GG fermented UHT-milk. Milchwissenschaft, 52, 675–8.Google Scholar
  101. Roudot-Algaron, F., Le Bars, D., Kerhoas, L., Einhorn, J. and Gripon, J.C. (1994) Phosphopeptides from Comte cheese: Nature and origin. J. Food Sci., 59, 544–7, 60.Google Scholar
  102. Sato, R., Noguchi, T. and Naito, H. (1983) The necessity for the phosphate portion of casein molecules to enhance Ca absorption from the small intestine. Agric. Biol. Chem., 47, 2415–7.Google Scholar
  103. Scanff, P., Yvon, M., Thirouin, S. and Pelissier, J.-P. (1992) Characterisation and kinetics of gastric emptying of peptides derived from milk proteins in the preruminant calf. J. Dairy Res., 59, 437–47.Google Scholar
  104. Schanbacher, F.L., Talhouk, R.S. and Murray, F.A. (1997) Biology and origin of bioactive peptides in milk. Liv. Prod. Sci., 50, 105–23.Google Scholar
  105. Schanbacher, F.L., Talhouk, R.S., Murray, F.A., Gherman, L.I. and Willett, L.B. (1998) Milk-borne bioactive peptides. Int. Dairy J., 8, 393–403.Google Scholar
  106. Shin, K., Yamauchi, K., Teraguchi, S., Hayasawa, H., Tomita, M., Otsuka, Y. and Yamazaki, S. (1998) Antibacterial activity of bovine lactoferrin and its peptides against enterohaemorragic E. coli O157:H7. Lett. Appl. Microbiol., 26, 407–11.Google Scholar
  107. Singh, T.K., Fox, P.F. and Healy, A. (1997) Isolation and identification of further peptides in the diafiltration retentate of the water soluble fraction of Cheddar cheese. J. Dairy Res., 64, 433–43.Google Scholar
  108. Smyth, M. and FitzGerald, R.J. (1998) Relationship between some characteristics of WPC hydrolysates, and the enzyme complement in commercially available proteinase preparations. Int. Dairy J., 8, 819–27.Google Scholar
  109. Suetsuna, K. and Osajima, K. (1989) Blood pressure reduction and vasodilatory effects in vivo of, peptides originating from sardine muscle (in Japanese). J. Jap. Soc. Nutr. Food Sci., 42, 47–54.Google Scholar
  110. Sutas, Y., Soppi, E., Korhonen, H., Syvaoja, E.-L., Saxelin, M., Rokka, T. and Isolauri, E. (1996) Suppression of lymphocyte proliferation in vitro by bovine caseins hydrolysed with Lactobacillus GG-derived enzymes. J. Allergy Clin. Immunol., 98, 216–24.Google Scholar
  111. Svedberg, J., de Haas, J., Leimenstoll, G., Paul, F. and Teschemacher, H. (1985) Demonstration of β-casomorphin immunoreactive materials in in vitro digests of bovine milk and in small intestine contents after bovine milk ingestion in adult humans. Peptides, 6, 825–30.Google Scholar
  112. Takano, T. (1998) Milk derived peptides and hypertension reduction. Int. Dairy J., 8, 375–81.Google Scholar
  113. Tani, F., Shiota, A., Chiba, H. and Yoshikawa, M. (1994) Serorphin, an opioid peptide derived from bovine serum albumin, in, β-Casomorphins and Related Peptides: Recent Developments. (V. Brantl and H. Teschemacher eds.) VCH, Weinheim, pp. 49–53.Google Scholar
  114. Teschemacher, H., Umbach, M., Hamel, U., Praetorius, K., Ahnert-Hilger, G., Brantl, V., Lottspeich, F. and Henschen, A. (1986) No evidence for the presence of β-casomorphins in human plasma after ingestion of cows’ milk or milk products. J. Dairy Res., 53, 135–8.Google Scholar
  115. Teschemacher, H. and Brantl, V. (1994) Milk protein derived atypical opioid peptides and related compounds with opioid antagonist activity, in, β-Casomorphins and Related Peptides: Recent Developments, (V. Brantl and H. Teschemacher eds.) VCH, Weinheim, pp. 3–17.Google Scholar
  116. Teschemacher, H., Koch, G. and Brantl, V. (1997) Milk protein-derived opioid receptor ligands. Biopoly., 43, 99–117.Google Scholar
  117. Tomé, D. and Debabbi, H. (1998) Physiological effects of milk protein components. Int. Dairy J., 8, 383–92.Google Scholar
  118. Tomé, D., Dumontier, A.M., Hautefeuille, M. and Desjeux, J.F. (1987) Opiate activity and transepithelial passage of intact β-casomorphins in rabbit ileum. Am. J. Physiol., 253, G737–44.Google Scholar
  119. Tomita, M., Bellamy, W., Takase, M., Yamauchi, K., Wakabayashi, H. and Kawase, K. (1991) Potent antibacterial peptides generated by pepsin digestion of bovine lactoferrin. J. Dairy Sci., 74, 4137–42.Google Scholar
  120. Tomita, M., Takase, M., Bellamy, W. and Shimämura, S. (1994) A review: the active peptide of lactoferrin. Acta Pediatr. Jpn., 36, 585–91.Google Scholar
  121. Umbach, M., Teschemacher, H., Praetorius, K., Hirschhauser, R., and Bostedt, H. (1985) Demonstration of a β-casomorphin immunoreactive material in the plasma of newborn calves after milk intake. Reg. Pep., 12, 223–30.Google Scholar
  122. West, D.W. (1986) Structure and function of the phosphorylated residues of casein. J. Dairy Res., 53, 333–52.Google Scholar
  123. Wyvratt, M.J. and Patchet, A.A. (1985) Recent developments in the design of angiotensin-converting enzyme inhibitors. Med. Res. Rev., 5, 485–531.Google Scholar
  124. Yamamoto, N., Akino, A. and Takano, T. (1994) Antihypertensive effects of peptides derived from casein by an extracellular proteinase from Lactobacillus helveticus CP790. J. Dairy Sci., 11, 917–22.Google Scholar
  125. Yamamoto, N. (1997) Antihypertensive peptides derived from food proteins. Biopoly., 43, 129–34.Google Scholar
  126. Yamamoto, N., Maeno, M. and Takano, T. (1999) Purification and characterisation of an antihypertensive peptide from yoghurt-like product fermented by Lactobacillus helveticus CPN4. J. Dairy Sci., 82, 1388–93.Google Scholar
  127. Yoshikawa, M., Tani, F., Yoshimura, T. and Chiba, H. (1986) Opioid peptides from milk proteins. Agric. Biol. Chem., 50, 2419–21.Google Scholar
  128. Yoshikawa, M., Tani, F., Shiota, H., Usui, H., Kurahashi, K. and Chiba, H. (1994) Casoxin D, an opioid antagonist/ileum-contracting/vasorelaxing peptide derived from human αs1-casein, in, β-Casomorphins and Related Peptides: Recent Developments, (V. Brantl and H. Teschemacher eds.) VCH, Weinheim, pp. 43–8.Google Scholar
  129. Ziodrou, C., Streaty, R.A. and Klee, W.A. (1979) Opioid peptides derived from food proteins. J. Biol. Chem., 254, 2446–9.Google Scholar
  130. Zucht, H.D., Raida, M., Andermann, K., Mägert, H.-J. and Forssman, W.G. (1995) Casocidin-I: a casein-αs2 derived peptide exhibits antibacterial activity. FEBS Lett., 372, 185–8.Google Scholar

Copyright information

© Springer Science+Business Media New York 2003

Authors and Affiliations

  • R. J. Fitzgerald
  • H. Meisel

There are no affiliations available

Personalised recommendations