Molecular and Cellular Biochemistry

, Volume 87, Issue 1, pp 5–30 | Cite as

Caseins of various origins and biologically active casein peptides and oligosaccharides: Structural and physiological aspects

  • Anne-Marie Fiat
  • Pierre Jollès


The first part of the present review is focused on structural aspects concerning the so far studied casein fractions of various origins: they are compared to the four classical major bovine caseins (σsl-, σs2- β- and κ). The calcium-sensitive casein fractions are always phosphorylated whereas κ-caseins are glycosylated. The study of the casein genes showed that the calcium-sensitive caseins diverged from a common ancestral gene and during the evolution, intergenic and intragenic duplications occurred. The considerable conservation of the phosphorylation sites emphasizes the importance of phosphorylated residues for the function of caseins, i.e. the formation of micelles and the binding of Ca2+. In κ-caseins all the prosthetic sugar groups are linked by O-glycosidic linkages: their number varies from 0 to 5 in bovine κ-casein and up to 10 in human κ-casein. The structures of the known κ-casein carbohydate moieties are described. Finally the milk clotting process (interaction κ-casein/chymosin) is compared to the blood clotting process (interaction fibrinogen/thrombin): a large number of similarities could be noted between both clotting phenomena.

The second part of the review is devoted to the study of short casein peptides endowed with various biological activities. Some of them behaved as immunomodulators or casomorphins or angiotensin I converting enzyme inhibitors; others demonstrated an effect on platelet functions. A ‘strategic zone’ containing immunostimulating and opioid peptides could be located in cow and human β-caseins. Furthermore bitter peptides, emulsifying peptides, calcium absorption enhancing peptides, chymosin-inhibiting peptides, have also been described and several further properties have been attributed to the κ-caseinoglycopeptide; two tetrasaccharides isolated from the latter possess blood group activities.

In conclusion caseins, the main milk proteins, should not only be considered as a nutriment but as a possible source of biologically active components.

If, in the future, some of the discussed active peptides cannot be characterized in vivo, they can all, nevertheless, be synthesized and used either as food additives or in pharmacology.

Key words

caseins biologically active casein peptides casein oligosaccharides casein structures immunomodulators platelet function 


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  1. 1.
    McKenzie HA: Milk Proteins Chemistry and Molecular Biology Vols I and II, Academic Press, New York, 1970–1971Google Scholar
  2. 2.
    Alais C, Blanc B: Milk proteins: biochemical and biological aspects. World Rev Nutr Diet 20:66–166, 1975Google Scholar
  3. 3.
    Jollès P: Progress in the chemistry of casein. Angew Chem Int Ed English 5:558–566, 1966Google Scholar
  4. 4.
    Jollès P: Glycoproteins. In: Gottschalk A. (ed) BBA Library, vol 5B Elsevier Amsterdam, 1972, pp 782–809Google Scholar
  5. 5.
    Ribadeau-Dumas B: Actualités dans le domaine de la connaissance de la structure et des propriétés biochimiques des protéines laitières. Rev Lait Fr 400:17–32, 1981Google Scholar
  6. 6.
    Eigel WN, Butler JE, Ernstrom CA, Farrel HM, Harwalkar VR, Jenness R, Whitney RMcL: Nomenclature of proteins of cow's milk: fifth revision. J Dairy Sci 67:1599–1631, 1984Google Scholar
  7. 7.
    Lenoir J: Les caséines du lait. Rev Lait Fr 440:17–23, 1985Google Scholar
  8. 8.
    Waugh DF: Milk proteins chemistry and molecular biology. In: McKenzie HA (ed) Vol II, Academic Press, New York, pp 3–85, 1970–1971Google Scholar
  9. 9.
    Topper YJ: Multiple hormone interactions in the development of mammary gland in vitro. Rec Prog Horm Res 26:286–308, 1970Google Scholar
  10. 10.
    Mercier JC, Grosclaude F, Ribadeau-Dumas B: Structure primaire de la caseine α1s-bovine. Séquence complete. Eur J Biochem 23:41–51, 1971Google Scholar
  11. 11.
    Grosclaude F, Joudrier P, Mahé MR Polymorphisme de la caseine αs2 bovine: étroite liaison du locus αs2-Cn avec les loci αsl-Cn, β-Cn et K-Cn: mise en evidence d'une deletion dans le variant αs2-Cn D. Ann Genet sél anim 10:313–327, 1978Google Scholar
  12. 12.
    Brignon G, Ribadeau-Dumas B, Mercier JC, Pelissier JP: Complete amino acid sequence of bovine αs2-casein. FEBS Lett 76:274–279, 1977Google Scholar
  13. 13.
    Grosclaude F, Mahé MF, Mercier JC, Ribadeau-Dumas B: Caractérisation des variants génétiques des caseines αsl et β bovines. Eur J Biochem 26:328–337, 1972Google Scholar
  14. 14.
    Ribadeau-Dumas B, Brignon G, Grosclaude F, Mercier JC: Structure primaire de la caseine β bovine. Sequence complete. Eur J Biochem 25:505–514, 1972Google Scholar
  15. 15.
    Petrilli P, Addeo F, Chianese L: Primary structure of water buffalo β-casein tryptic and CNBr peptides. Ital J Biochem 32:336–344, 1983Google Scholar
  16. 16.
    Greenberg R, Groves ML, Dower HJ: Human β-casein. Amino acid sequence and identification of phosphorylation sites. J Biol Chem 259:5132–5138, 1984Google Scholar
  17. 17.
    Delfour A, Jolles J, Alais C, Jolles P: Caseinoglycopeptides characterization of a methionine residue and of the Nterminal sequence. Biochem Biophys Res Commun 19:452–455, 1965Google Scholar
  18. 18.
    Delfour A, Alais C, Jolles P: Structure of cow's κ-caseinoglycopeptide: the N-terminal octadecapeptide. Chimia 20:148–150, 1966Google Scholar
  19. 19.
    Jollès J, Schoentgen F, Alais C, Fiat AM, Jolles P: Studies on the primary structure of cow κ-casein. Structural features of para-κ-casein; N-terminal sequence of Kcaseinoglycopeptide studied with a sequencer. Helv Chim Acta 55:2872–2883, 1972Google Scholar
  20. 20.
    Mercier JC, Brignon G, Ribadeau-Dumas B: Structure primaire de la caseine κ B bovine. Sequence complete. Eur J Biochem 35:222–235, 1973Google Scholar
  21. 21.
    Brignon G, Chtourou A, Ribadeau-Dumas B: Preparation and amino acid sequence of human κ-casein. FEBS Lett 188:48–54, 1985Google Scholar
  22. 22.
    Jolles J, Schoentgen F, Hermann J, Alais C, Jollès P: The sequence of sheep κ-casein: primary structure of para-κAcasein. Eur J Biochem 46:127–132, 1974Google Scholar
  23. 23.
    Jollès J, Fiat AM, Schoentgen F, Alais C, Jollès P: The amino acid sequence of sheep κA-casein. II Sequence studies concerning the κA-caseinoglycopeptide and establishment of the complete primary structure of the protein. Biochem Biophys Acta 365:335–343, 1974Google Scholar
  24. 24.
    Mercier JC, Addeo F, Pelissier JP: Structure du caseinomacropeptide de la caseine κ caprine. Biochimie 58:1303–1310, 1976Google Scholar
  25. 25.
    Mercier JC, Chobert JM, Addeo F: Comparative study of the caseinomacropeptide from seven species. FEBS Lett 72:208–214, 1976Google Scholar
  26. 26.
    Jolles J, Alais C, Jollès P: Chemical structure studies of cow IC-casein: study of the soluble tryptic peptides. Helv Chim Acta 53:1918–1926, 1970Google Scholar
  27. 27.
    Mercier JC, Uro J, Ribadeau-Dumas B, Grosclaude F: Structure primaire du caséinomacropeptide de la caséine κ B1 bovine. Eur J Biochem 27:535–547, 1972Google Scholar
  28. 28.
    Brignon G, Mercier JC, Ribadeau-Dumas B, Das BC: Structure primaire de la paracaséine kappa bovine. FEBS Lett 27:301–305, 1972Google Scholar
  29. 29.
    Chobert JM, Mercier JC, Bahy C, Hazé G: Structure primaire du caséinomacropeptide des caséines κ porcine et humaine. FEBS Lett 72:173–178, 1976Google Scholar
  30. 30.
    Mercier JC, Gaye P: Study of secretory lactoproteins: primary structures of the signals and enzymatic processing. Annals NY Acad Sci 343:232–251, 1980Google Scholar
  31. 31.
    Hobbs AA, Rosen JM: Sequence of rat α- and γ-casein mRNAs: evolutionary comparison of the calciumdependent rat casein multigene family. Nucleic Acids Res 10:8079–8098, 1982Google Scholar
  32. 32.
    Blackburn DE, Hobbs AA, Rosen JM: Rat β-casein cDNA: sequence analysis and evolutionary comparisons. Nucleic Acids Res 10:2295–2307, 1982Google Scholar
  33. 33.
    Nakhasi HL, Grantham FH, Gullino PM: Expression of Kcasein in normal and neoplastic rat mammary gland is under the control of prolactin. J Biol Chem 259:14894–14898, 1984Google Scholar
  34. 34.
    Hall L, Laird JE, Pascall JC, Craig RK: Guinea-pig casein A cDNA-nucleotide sequence analysis and comparison of the deduced protein sequence with that of bovine αs2-casein. Eur J Biochem 138:585–589, 1984Google Scholar
  35. 35.
    Hall L, Laird JE, Craig RK: Nucleotide sequence determination of guinea-pig casein B mRNA reveals homology with bovine and rat αs1-caseins and conservation of the noncoding regions of the mRNA. Biochem J 222:561–570, 1984Google Scholar
  36. 36.
    Hennighausen LG, Stendle A, Sippel AE: Nucleotide sequence of cloned cDNA coding for mouse ε-casein. Eur J Biochem 126:569–572, 1982Google Scholar
  37. 37.
    Thompson MD, Dave JR, Nakhasi HL: Molecular cloning of mouse mammary gland K-casein: comparison with rat κ-casein and rat and human γ-fibrinogen. DNA 4:263–271, 1985Google Scholar
  38. 38.
    Mercier JC, Gaye P, Soulier S, Hue-Delahare D, Vilotte JL: Construction and identification of recombinant plasmids carrying cDNAs coding for ovine αs1-, αs2-, β-, κ-casein and β-lactoglobulin. Nucleotide sequence of αs1-casein cDNA. Biochimie 67:959–971, 1985Google Scholar
  39. 39.
    Boisnard M, Petrissant G: Complete sequence of ovine αs2-casein messenger RNA. Biochimie 67:1043–1051, 1985Google Scholar
  40. 40.
    Stewart AF, Willis IM, Mackinlay AG: Nucleotide sequences of bovine αs1- and κ-casein cDNAs. Nucl Acid Res 12:3895–3907, 1984Google Scholar
  41. 41.
    Jimenez-Flores R, Kang YC, Richardson T: Cloning and sequence analysis of bovine β-casein cDNA. Biochem Biophys Res Commun 142:617–621, 1987Google Scholar
  42. 42.
    Stewart AF, Bonsing J, Beattie CW, Shah F, Willis IM, Mackinlay AG: Complete nucleotide sequences of bovine αs2 and β-casein cDNAs: comparisons with related sequences in other species. Mol Biol Evol 4:231–241, 1987Google Scholar
  43. 43.
    Grosclaude F, Mercier JC, Ribadeau-Dumas B: Genetic aspects of cattle casein research. Neth Milk Dairy J 27:328–340, 1973Google Scholar
  44. 44.
    Gupta P, Rosen JM, d'Eustachio P, Ruddle FH: Localization of the casein gene family to a single mouse chromosome. J Cell Biol 93:199–204, 1982Google Scholar
  45. 45.
    Jones WK, Yu-Lee LY, Clift SM, Brown TL, Rosen JM: The rat casein multigene family fine structure and evolution of the β-casein gene. J Biol Chem 260:7042–7050, 1985Google Scholar
  46. 46.
    Ly YL, Rosen JM: The rat casein multigenic family 1. Fine structure of the γ-casein gene. J Biol Chem 258:10794–10804, 1983Google Scholar
  47. 47.
    Mercier JC: Phosphorylation of caseins, present evidence for an amino acid triplet code post translationally recognized by specific kinases. Biochimie 63:1–17, 1981Google Scholar
  48. 48.
    Malpress FH, Seid-Akhavan M: Studies on human αs and κ-casein fractions and human caseinoglycomacropeptide. Biochem J 101:764–773, 1966Google Scholar
  49. 49.
    Fiat AM, Alais C, Jolles P: Contribution to the study of the linkage between the peptide and sugar moieties in cow's κcasein. Chimia 22:137–139, 1968Google Scholar
  50. 50.
    Jollès J, Fiat AM, Alais C, Jollès P: Comparative study of cow and sheep κ-caseinoglycopeptides: determination of the N-terminal sequences with a sequencer and location of the sugars. FEBS Lett 30:173–175, 1973Google Scholar
  51. 51.
    Fiat AM, Jolles J, Loucheux-Lefebvre MH, Alais C, Jolles P: Localisation of the prosthetic sugar groups of bovine colostrum κ-casein. Hoppe-Seyler's Z Physiol Chem 362:1447–1454, 1981Google Scholar
  52. 52.
    Kanamori M, Kawaguchi N, Ibuki F, Doi H: Attachment sites of carbohydrate moieties to peptide chain of bovine κ- from normal milk. Agric Biol Chem 44:1855–1861, 1980Google Scholar
  53. 53.
    Kanamori M, Doi H, Ideno S, Ibuki F: Presence of Oglycosidic linkage through serine residue in κ-casein component from bovine mature milk. J Nutr Sci Vitaminol 27:231–241, 1981Google Scholar
  54. 54.
    Doi H, Kobatake H, Ibuki F, Kanamori M: Attachment sites of carbohydrate portions to peptide chain of κ-casein from bovine colostrum. Agric Biol Chem 44:2605–2611, 1980Google Scholar
  55. 55.
    Zevaco C, Ribadeau-Dumas B: A study on the carbohydrate binding sites of bovine κ-casein using high performance liquid chromatography. Milchwissenschaft 39:206–210, 1984Google Scholar
  56. 56.
    Vreeman HJ, Visser S, Slangen CJ, van Riel JAM: Characterization of bovine κ-casein fractions and the kinetics of chymosin-induced macropeptide release from carbohydrate-free and carbohydrate-containing fractions determined by high-performance gel-permeation chromatography. Biochem J 240:87–97, 1986Google Scholar
  57. 57.
    Chou PY, Fasman GD: Conformational parameters for amino acid in helical, β-sheet and random coil regions calculated from proteins. Biochemistry 13:222–245, 1974Google Scholar
  58. 58.
    Loucheux-Lefebvre MH, Aubert JP, Jollès P: Prediction of the conformation of the cow and sheep κ-caseins. Biophys J 23:323–336, 1978Google Scholar
  59. 59.
    Fiat AM, Jollès J, Aubert JP, Loucheux-Lefebvre MH, Jollès P: Localisation and importance of the sugar part of human casein. Eur J Biochem 111:333–339, 1980Google Scholar
  60. 60.
    Jollès P, Alais C, Adam A, Delfour A, Jolles J: Recherches préliminaires sur la structure de la partie glucidique des caseinoglycopeptides. Chimia 18:357–358, 1964Google Scholar
  61. 61.
    Fournet B, Fiat AM, Montreuil J, Jolles P: The sugar part of κ-caseins from cow milk and colostrum and its microheterogeneity. Biochimie 57:161–165, 1975Google Scholar
  62. 62.
    Fournet B, Fiat AM, Alais C, Jolles P: Cow κ-casein: structure of the carbohydrate portion. Biochim Biophys Acta 576:339–346, 1979Google Scholar
  63. 63.
    Van Halbeek H, Dorland L, Vliegenthart JFG, Fiat AM, Jolles P: A 360-MHZ 1H-NMR study of three oligosaccharides isolated from cow κ-casein. Biochim Biophys Acta 623:295–300, 1980Google Scholar
  64. 64.
    Guérin J, Alais C, Jollès J, Jollès P: κ-Casein from bovine colostrum. Biochim Biophys Acta 351:325–332, 1974Google Scholar
  65. 65.
    Saito T, Itoh T, Adachi S, Suzuki T, Usui T: The chemical structure of neutral and acidic sugar chains obtained from bovine colostrum κ-casein. Biochim Biophys Acta 678:257–267, 1981Google Scholar
  66. 66.
    Saito T, Itoh T, Adachi S: The chemical structure of a tetrasaccharide containing N-acetyl glucosamine obtained from bovine colostrum κ-casein. Biochim Biophys Acta 673:487–494, 1981Google Scholar
  67. 67.
    Saito T, Itoh T, Adachi S, Suzuki T, Usui T: A new hexasaccharide chain isolated from bovine colostrum κ-casein taken at the time of parturition. Biochim Biophys Acta 719:309–317, 1982Google Scholar
  68. 68.
    Van Halbeek H, Dorland L, Vliegenthart JFG, Fiat AM, Jolles P: Structural characterization of a novel acidic oligosaccharide unit derived from cow colostrum κ-casein. A 500 MHz 1H-NMR study. FEBS Lett 133:45–50, 1981Google Scholar
  69. 69.
    Fiat AM, Chevan J, Jolles P, De Waard P, Vliegenthart JFG, Piller F, Cartron JP: Structural variability of the neutral carbohydrate moiety of cow colostrum κ-casein as a function of time after parturition. Identification of a tetrasaccharide with blood group I specificity. Eur J Biochem 173:253–259, 1988Google Scholar
  70. 70.
    Soulier S, Sarfati RS, Szabo L: Structure of the asialyl oligosaccharide chains from ovine κ-caseins. 2. Sequence analysis of three oligosaccharide colostrum. Eur J Biochem 108:465–472, 1980Google Scholar
  71. 71.
    Van Halbeek H, Vliegenthart JFG, Fiat AM, Jolles P: Isolation and structural characterization of the smaller-size oligosaccharides from desialylated human κ-casein. Estab lishment of a novel type of core for a mucin-type carbohydrate chain. FEBS Lett 187:81–88, 1985Google Scholar
  72. 72.
    Saito T, Itoh T, Adachi S: Chemical structure of neutral sugar chains isolated from human mature milk κ-casein. Biochim Biophys Acta 964:213–220, 1988Google Scholar
  73. 73.
    Slattery CW: Variation in the glycosylation pattern of bovine κ-casein with micelle size and its relationship to a micelle model. Biochemistry 17:1100–1104, 1978Google Scholar
  74. 74.
    Carroll RJ, Farrell HM: Immunological approach to location of κ-casein in the casein micelle by electron microscopy. J Dairy Sci 66:679–686, 1983Google Scholar
  75. 75.
    Creamer LK, Wheelock JV, Samuel D: The distribution of glyco-κ-casein and carbohydrate free-κ-casein between large and small bovine casein micelles and its implication in micelle structure. Biochim Biophys Acta 317:202–206, 1976Google Scholar
  76. 76.
    Dalgleish DG: Glycosylated κ-caseins and the sizes of bovine casein micelles. Analysis of the different forms of κ-casein. Biochim Biophys Acta 830:213–215, 1985Google Scholar
  77. 77.
    Horisberger M, Rouvet Vauthey M: Localization of glycosylated κ-casein on thin sections of casein micelles by lectin-labelled gold markers. Histochemistry 80:523–526, 1984Google Scholar
  78. 78.
    Addeo F, Martin P, Ribadeau-Duma B: Susceptibility of buffalo and cow κ-caseins to chymosin action. Milchwissenschaft 39:202–205, 1984Google Scholar
  79. 79.
    Doi H, Kawaguchi N, Ibuki F, Kanamori M: Susceptibility of kappa-casein components to various proteases. J Nutr Sci Vitaminol 25:33–41, 1979Google Scholar
  80. 80.
    Van Hooydonck ACM, Olieman C, Hagedoorn HG: Kinetics of the chymosin-catalysed proteolysis of kappa-casein in milk. Neth Milk Dairy J 38:207–222, 1984Google Scholar
  81. 81.
    Sinkinson G, Wheelock JV: Carbohydrates of the glycopeptides released by the action of rennin on whole milk. Biochim Biophys Acta 215:517–521, 1970Google Scholar
  82. 82.
    Jollès P, Henschen A: Comparison between the clotting of blood and milk. TIBS 7:325–328, 1982Google Scholar
  83. 83.
    Jollès P, Loucheux-Lefebvre MH, Henschen A: Structural relatedness of κ-casein and fibrinogen γ-chain. J Mol Evol 11:271–277, 1978Google Scholar
  84. 84.
    Brantl V, Teschemacher H, Henschen A, Lottspeich F: Novel opioid peptides derived from casein (β-casomorphins). I. Isolation from bovine casein peptone. Hoppe-Seyler's Z Physiol Chem 360:1211–1216, 1979Google Scholar
  85. 85.
    Brantl V, Teschemacher H, Bläsig J, Henschen A, Lottspeich F: Opioid activities of β-casomorphins. Life Sci 28:1903–1909, 1981Google Scholar
  86. 86.
    Chang KJ, Cuatrecasas P, Wei ET, Chang JK: Analgesic activity of intracerebroventricular administration of morphiceptin and β-casomorphins: correlation with the morphin (μ)receptor binding affinity. Life Sci 30:1547–1551, 1982Google Scholar
  87. 87.
    Grecksch G, Schweigert C, Matthies H: Evidence for analgesic activity of β-casomorphin in rats. Neurosci Lett 27:325–328, 1981Google Scholar
  88. 88.
    Kreil G, Umbach M, Brantl V, Teschemacher H: Studies on the enzymatic degradation of β-casomorphins. Life Sci 33:137–140, 1983Google Scholar
  89. 89.
    Petrilli P, Picone D, Caporale C, Addeo F, Auricchio S, Marino G: Does casomorphin have a functional role? FEBS Lett 169:53–56, 1984Google Scholar
  90. 90.
    Caporale C, Fontanella A, Petrilli P, Pucci P, Molinaro MF, Picone D, Auricchio S: Isolation and characterization of dipeptidyl peptidase I V from human meconium. Functional role of β-casomorphins. FEBS Lett 184:273–277, 1985Google Scholar
  91. 91.
    Ermisch A, Rühle HJ, Neubert K, Hartrodt B, Landgraf R: On the blood brain barrier to peptides: [3H] β-casomorphin-5 uptake by eighteen brain regions in vivo. J Neurochem 41:1229–1233, 1983Google Scholar
  92. 92.
    Svedberg J, de Haas J, Leimenstoll G, Paul F, Teschemacher H: 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 6:825–830, 1985Google Scholar
  93. 93.
    Matthies H, Stark H, Hartrodt B, Ruetrich HL, Spieler HT, Barth A, Neubert K: Derivatives of β-casomorphins with high analgesic potency. Peptides 5:463–470, 1984Google Scholar
  94. 94.
    Chang KJ, SU YF, Brent DA, Chang DK: Isolation of a specific μ-opiate receptor peptide, morphiceptin from an enzymatic digest of milk proteins. J Biol Chem 260:9706–9712, 1985Google Scholar
  95. 95.
    Zioudrou C, Streaty RA, Klee WA: Opioid peptides derived from food proteins. J Biol Chem 254:2446–2449, 1979Google Scholar
  96. 96.
    Loukas S, Varoucha D, Zioudrou C, Streaty RA, Klee WA: Opioid activities and structures of α-casein-derived exorphins. Biochemistry 22:4567–4573, 1983Google Scholar
  97. 97.
    Yoshikawa M, Tani F, Ashikaga T, Yoshimura T, Chiba H: Purification and characterization of an opioid antagonist from a peptic digest of bovine κ-casein. Agric Biol Chem 50:2951–2954, 1986Google Scholar
  98. 98.
    Plotnikoff NP, Murgo AJ, Miller GC, Corder CN, Faith RE: Enkephalins: immunomodulators. Fed Proc 44:118–122, 1985Google Scholar
  99. 99.
    Plotnikoff NP, Miller GC, Solomon SKT, Faith RE, Edwards LD, Murgo AJ: Methionine-enkephalin: immunomodulation in normal volunteers (in vivo). Psychopharmacol Bull 22:1097–1100, 1986Google Scholar
  100. 100.
    Wybran J, Appelboom T, Famacy JP, Govaerts A: Suggestive evidence for receptors for morphine and methionineenkephalin on normal human T lymphocytes. J Immun 123:1068–1070, 1979Google Scholar
  101. 101.
    Lopker A, Abood LG, Hoss W, Lionetti FJ: Stereoselective muscarinic acetylcholine and opiate receptors in human phagocytic leukocytes. Biochem Pharmacol 29:1361–1365, 1980Google Scholar
  102. 102.
    Migliore-Samour D, Jolles P: Casein, a prohormone with an immunomodulating role for the newborn? Experientia 44:188–193, 1988Google Scholar
  103. 103.
    Parker F, Migliore-Samour D, Floc'h F, Zerial A, Werner GH, Jolles J, Casaretto M, Zahn H, Jolles P: Immunostimulating hexapeptide from human casein: amino acid sequence, synthesis and biological properties. Eur J Biochem 145:677–682, 1984Google Scholar
  104. 104.
    Berthou J, Migliore-Samour D, Lifchitz A, Delettré J, Floc'h F, Jolles P: Immunostimulating properties and threedimensional structure of tripeptides from human and cow caseins. FEBS Lett 218:55–58, 1987Google Scholar
  105. 105.
    Gattegno L, Migliore-Samour D, Saffar L, Jollès P: Influence sur l'immunité de quelques éléments nutritionnels. Les Entretiens de Bobigny: 141–144, 1987Google Scholar
  106. 106.
    Aoki K, Kajiwara M, Oka T: The role of bestatin-sensitive aminopeptidase angiotensin converting enzyme and thiorphan sensitive ‘enkephalinase’ in the potency of enkephalins in the guinea-pig ileum. Japan J Pharmacol 36:59–65, 1984Google Scholar
  107. 107.
    Paegelow I, Werner H: Immunomodulation by some oligopeptides. Meth and Find Exptl Clin Pharmacol 8:91–95, 1986Google Scholar
  108. 108.
    Maruyama S, Mitachi H, Tanaka H, Tomizuka N, Suzuki H: Studies on the active site and antihypertensive activity of angiotensin I-converting enzyme inhibitors derived from casein. Agric Biol Chem 51:1581–1586, 1987Google Scholar
  109. 109.
    Maruyama S, Mitachi H, Awaya J, Kurono M, Tomizuka N, Suzuki H: Angiotensin I-converting enzyme inhibitory activity of the C-terminal hexapeptide of αsl-casein. Agric Biol Chem 51:2557–2561, 1987Google Scholar
  110. 110.
    Henriques OB, de Deus RB, Santos RAS: Bradykinin potentiating peptides isolated from α-casein tryptic hydrolysate. Biochem Pharmacol 36:182–184, 1987Google Scholar
  111. 111.
    Kloczewiak M, Timmons S, Lukas TJ, Hawiger J: Platelet receptor recognition sites on human fibrinogen. Synthesis and structure-function relationship of peptides correspond ing to the carboxyterminal segment of the γ-chain. Biochemistry 23:1767–1774, 1984Google Scholar
  112. 112.
    Jollès P, Lévy-Toledano S, Fiat AM, Soria C, Gillessen D, Thomaidis A, Dunn FW Caen JP: Analogy between fibrinogen and casein. Effect of an undecapeptide isolated from κ-casein on platelet function. Eur J Biochem 158:379–384, 1986Google Scholar
  113. 113.
    Minamiura N, Matsumura Y, Fukumoto J, Yamamoto T: Bitter peptides in cow milk casein digests with bacterial proteinase. I Isolation and determination of amino acid se quence of a bitter peptide. Agric Biol Chem 36:588–595, 1972Google Scholar
  114. 114.
    Minamiura N, Matsumura Y, Yamamoto T: Bitter peptides in the casein digests with bacterial proteinase. II A bitter peptide consisting of tryptophan and leucine. J Biochem (Tokyo) 72:841–848, 1972Google Scholar
  115. 115.
    Matoba T, Nagayasu C, Hayashi R, Hata T: Bitter peptides in tryptic hydrolysate of casein. Agric Biol Chem 33:1662–1663, 1969Google Scholar
  116. 116.
    Van Leeuwen HJ: Removal of a bitter peptide from tryptic hydrolysates of casein coprecipitate by immuno adsorbent affinity chromatography. Agric Biol Chem 42:1375–1378, 1978Google Scholar
  117. 117.
    Sato R, Noguchi T, Naito H: Casein phosphopeptide (CPP) enhances calcium absorption from the ligated segment of rat small intestine. J Nutr Sci Vitaminol 32:67–76, 1986Google Scholar
  118. 118.
    Lee SW, Shimizu M, Kaminogawa S, Yamauchi K: Emulsifying properties of a mixture of peptides derived from the enzymatic hydrolyzates of bovine caseins. Agric Biol Chem 51:1535–1540, 1987Google Scholar
  119. 119.
    Yvon M, Pelissier JP: Characterization and kinetics of evacuation of peptides resulting from casein hydrolysis in the stomach of the calf. J Agric and Food Chem 35:148–156, 1987Google Scholar
  120. 120.
    Stan EY, Chernikov MP: Formation of a peptide inhibitor of gastric secretion from rat milk proteins in vivo. Bull Exp Biol Med (Engl Transl) 94:1087–1089, 1982Google Scholar
  121. 121.
    Lahav E: presented at the International Dairy Federation, Annual Sessions, Tel Aviv, Sept 1987Google Scholar
  122. 122.
    Bezkorovainy A, Grohlich JD, Nichols JH: Isolation of a glycopeptide fraction with Lactobacillus bifidus subspecies pennsylvanicus growth-promoting activity from whole human milk casein. Amer J Clin Nutr 32:1428–1432, 1979Google Scholar
  123. 123.
    Azuma N, Yamauchi K, Mitsuoka T: Bifidus growthpromoting activity of a glycomacropeptide derived from human κ-casein. Agric Biol Chem 48:2159–2162, 1984Google Scholar
  124. 124.
    Fiat AM, Goussault Y, Font J, Jollèss P: Antigénicité croisée des caseinoglycopeptides κ de vache et de brebis avec les antigènes des groupes sanguins M et N. Immunochemistry 10:355–357, 1973Google Scholar
  125. 125.
    Agunod M, Yamaguchi N, Lopez R, Luhby AL, Glass GB: Correlative study of hydrochloric acid, pepsin and IF secretion in newborn and infants. Am J Dig Dis 14:400–414, 1969Google Scholar
  126. 126.
    Mason S: Some aspects of gastric function in the newborn. Archs Dis Childh 37:387–391, 1962Google Scholar
  127. 127.
    Berfenstam R, Jagenburg R, Mellander O: Protein hydrolysis in the stomach of premature and full-term infants. Acta paediat 44:348–354, 1955Google Scholar
  128. 128.
    Jollès P, Parker F, Floc'h F, Migliore D, Alliel P, Zerial A, Werner GH: Immunostimulating substances from human casein. J Immunopharmacol 4:363–369, 1982Google Scholar
  129. 129.
    Ogra SS, Weintraub D, Ogra PL: Immunologic aspects of human colostrum and milk. III. Fate and absorption of cellular and soluble components in the gastrointestinal tract of the newborn. J Immun 119:245–248, 1977Google Scholar
  130. 130.
    Robertson DH, Paganelli R, Dinwiddie R, Levinsky RJ: Milk antigen absorption in the preterm and term neonate. Archs Dis Childh 57:369–372, 1982Google Scholar
  131. 131.
    Koch G, Wiedemann K, Zimmermann W: Human β (1–8) immunoreactive materials in the plasma of nursing mothers. Poster/Friihjahrstagung der Deutschen Pharmakologischen Gesellschaft, Mainz 1986Google Scholar
  132. 132.
    Umbach M, Teschemacher H, Praetorius K, Hirshhäusser R, Bostedt H: Demonstration of a β-casomorphin immunoreactive material in the plasma of newborn calves after milk intake. Reg Pept 12:223–230, 1985Google Scholar

Copyright information

© Kluwer Academic Publishers 1989

Authors and Affiliations

  • Anne-Marie Fiat
    • 1
  • Pierre Jollès
    • 1
  1. 1.Laboratory of Proteins (UA CNRS No 1188)University of Paris VParis CedexFrance

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