A comprehensive review on preparation, structure-activities relationship, and calcium bioavailability of casein phosphopeptides

References

• Adamson, N. J., and E. C. Reynolds. 1995. High performance capillary electrophoresis of casein phosphopeptides containing 2-5 phosphoseryl residues: Relationship between absolute electrophoretic mobility and peptide charge and size. Electrophoresis 16 (4):525–8. doi: 10.1002/elps.1150160186.
   PubMed Web of Science ®Google Scholar
• Adamson, N. J., and E. C. Reynolds. 1996. Characterization of casein phosphopeptides prepared using alcalase: Determination of enzyme specificity. Enzyme and Microbial Technology 19 (3):202–7. doi: 10.1016/0141-0229(95)00232-4.
   PubMed Web of Science ®Google Scholar
• Adamson, N. J., and E. C. Reynolds. 1997. Relationship between degree of casein hydrolysis and phosphopeptide release. The Journal of Dairy Research 64 (4):505–14. doi: 10.1017/s0022029997002483.
   PubMed Web of Science ®Google Scholar
• Adamson, N., P. F. Riley, and E. C. Reynolds. 1993. The analysis of multiple phosphoseryl-containing casein peptides using capillary zone electrophoresis. Journal of Chromatography 646 (2):391–6. doi: 10.1016/0021-9673(93)83352-S.
   PubMed Web of Science ®Google Scholar
• Adluri, R. S., L. Zhan, M. Bagchi, N. Maulik, and G. Maulik. 2010. Comparative effects of a novel plant-based calcium supplement with two common calcium salts on proliferation and mineralization in human osteoblast cells. Molecular and Cellular Biochemistry 340 (1–2):73–80. doi: 10.1007/s11010-010-0402-0.
   PubMed Web of Science ®Google Scholar
• Adolphi, B., K. E. Scholz-Ahrens, M. de Vrese, Y. Açil, C. Laue, and J. Schrezenmeir. 2009. Short-term effect of bedtime consumption of fermented milk supplemented with calcium, inulin-type fructans and caseinphosphopeptides on bone metabolism in healthy, postmenopausal women. European Journal of Nutrition 48 (1):45–53. doi: 10.1007/s00394-008-0759-y.
   PubMed Web of Science ®Google Scholar
• Amasheh, S., T. Schmidt, M. Mahn, P. Florian, J. Mankertz, S. Tavalali, A. H. Gitter, J. D. Schulzke, and M. Fromm. 2005. Contribution of claudin-5 to barrier properties in tight junctions of epithelial cells. Cell and Tissue Research 321 (1):89–96. doi: 10.1007/s00441-005-1101-0.
   PubMed Web of Science ®Google Scholar
• Areco, V., M. A. Rivoira, V. Rodriguez, A. M. Marchionatti, A. Carpentieri, and D. T. N. Tolosa. 2015. Dietary and pharmacological compounds altering intestinal calcium absorption in humans and animals. Nutrition Research Reviews 28 (2):83–99. doi: 10.1017/S0954422415000050.
   PubMed Web of Science ®Google Scholar
• Bao, X., X. Yuan, G. Feng, M. Zhang, and S. Ma. 2021. Structural characterization of calcium-binding sunflower seed and peanut peptides and enhanced calcium transport by calcium complexes in Caco-2 cells. Journal of the Science of Food and Agriculture 101 (2):794–804. doi: 10.1002/jsfa.10800.
   PubMed Web of Science ®Google Scholar
• Bass, J. K., and G. M. Chan. 2006. Calcium nutrition and metabolism during infancy. Nutrition (Burbank, Los Angeles County, Calif.) 22 (10):1057–66. doi: 10.1016/j.nut.2006.05.014.
   PubMed Web of Science ®Google Scholar
• Baum, F., J. Ebner, and J. Ebner. 2013. Identification of multiphosphorylated peptides in milk. Journal of Agricultural and Food Chemistry 61 (38):9110–7. doi: 10.1021/jf401865q.
   PubMed Web of Science ®Google Scholar
• Best, B. R. 2017. Computational and theoretical advances in studies of intrinsically disordered proteins. Current Opinion in Structural Biology 42:147–54. doi: 10.1016/j.sbi.2017.01.006.
   PubMed Web of Science ®Google Scholar
• Bonomi, M., G. T. Heller, C. Camilloni, and M. Vendruscolo. 2017. Principles of protein structural ensemble determination. Current Opinion in Structural Biology 42:106–16. doi: 10.1016/j.sbi.2016.12.004.
   PubMed Web of Science ®Google Scholar
• Bottani, M., S. Cattaneo, V. Pica, M. Stuknytė, I. D. Noni, and S. Cattaneo. 2020. In vitro antioxidant properties of digests of hydrolyzed casein and caseinophosphopeptide preparations in cell models of human intestine and osteoblasts. Journal of Functional Foods 64:103673. doi: 10.1016/j.jff.2019.103673.
   Web of Science ®Google Scholar
• Bronner, F. 2009. Recent developments in intestinal calcium absorption. Nutrition Reviews 67 (2):109–13. doi: 10.1111/j.1753-4887.2008.00147.x.
   PubMed Web of Science ®Google Scholar
• Bronner, F., and D. Pansu. 1999. Nutritional aspects of calcium absorption. The Journal of Nutrition 129 (1):9–12. doi: 10.1093/jn/129.1.9.
   PubMed Web of Science ®Google Scholar
• Cai, F., D. J. Manton, P. Shen, G. D. Walker, K. J. Cross, Y. Yuan, C. Reynolds, and E. C. Reynolds. 2007. Effect of addition of citric acid and casein phosphopeptide-amorphous calcium phosphate to a sugar-free chewing gum on enamel remineralization in situ. Caries Research 41 (5):377–83. doi: 10.1159/000104796.
   PubMed Web of Science ®Google Scholar
• Cao, Y., J. Miao, G. Liu, Z. Luo, Z. Xia, F. Liu, M. Yao, X. Cao, S. Sun, Y. Lin, et al. 2017. Bioactive peptides isolated from casein phosphopeptides enhance calcium and magnesium uptake in Caco-2 cell monolayers. Journal of Agricultural and Food Chemistry 65 (11):2307–14. doi: 10.1021/acs.jafc.6b05711.
   PubMed Web of Science ®Google Scholar
• Chen, D., X. Mu, H. Huang, R. Nie, Z. Liu, and M. Zeng. 2014. Isolation of a calcium-binding peptide from tilapia scale protein hydrolysate and its calcium bioavailability in rats. Journal of Functional Foods 6:575–84. doi: 10.1016/j.jff.2013.12.001.
   Web of Science ®Google Scholar
• Cosentino, S., C. Gravaghi, E. Donetti, B. M. Donida, G. Lombardi, M. Bedoni, A. Fiorilli, G. Tettamanti, and A. Ferraretto. 2010. Caseinphosphopeptide-induced calcium uptake in human intestinal cell lines HT-29 and Caco2 is correlated to cellular differentiation. The Journal of Nutritional Biochemistry 21 (3):247–54. doi: 10.1016/j.jnutbio.2008.12.016.
   PubMed Web of Science ®Google Scholar
• Cross, K. J., N. L. Huq, W. Bicknell, and E. C. Reynolds. 2001. Cation-dependent structural features of beta-casein-(1-25). The Biochemical Journal 356 (Pt 1):277–86. doi: 10.1042/0264-6021:3560277.
   PubMedGoogle Scholar
• Cross, K. J., N. L. Huq, J. E. Palamara, J. W. Perich, and N. L. Huq. 2005. Physicochemical characterization of casein phosphopeptide-amorphous calcium phosphate nanocomplexes. The Journal of Biological Chemistry 280 (15):15362–9. doi: 10.1074/jbc.M413504200.
   PubMed Web of Science ®Google Scholar
• Cross, K. J., N. L. Huq, and E. C. Reynolds. 2007. Casein phosphopeptides in oral health–chemistry and clinical applications. Current Pharmaceutical Design 13 (8):793–800. doi: 10.2174/138161207780363086.
   PubMed Web of Science ®Google Scholar
• Cruz-Huerta, E., M. J. García-Nebot, B. Miralles, I. Recio, and M. J. García-Nebot. 2015. Caseinophosphopeptides released after tryptic hydrolysis versus simulated gastrointestinal digestion of a casein-derived by-product. Food Chemistry 168:648–55. doi: 10.1016/j.foodchem.2014.07.090.
   PubMed Web of Science ®Google Scholar
• Deracinois, B., A. Mateos, A. Romelard, A. Boulier, J. Auger, A. Baniel, R. Ravallec, and C. Flahaut. 2021. Partial-, double-enzymatic dephosphorylation and EndoGluC hydrolysis as an original approach to enhancing identification of casein phosphopeptides (CPPs) by mass spectrometry. Foods 10 (9):2134. doi: 10.3390/foods10092134.
   PubMed Web of Science ®Google Scholar
• Diaz, D. B. G., S. Guizzardi, and D. T. N. Tolosa. 2015. Molecular aspects of intestinal calcium absorption. World Journal of Gastroenterology 21 (23):7142–54. doi: 10.3748/wjg.v21.i23.7142.
   PubMed Web of Science ®Google Scholar
• Dupas, C., I. Adt, A. Cottaz, R. Boutrou, D. Molle, J. Jardin, T. Jouvet, and P. Degraeve. 2009. A chromatographic procedure for semi-quantitative evaluation of caseinphosphopeptides in cheese. Dairy Science and Technology 89 (6):519–29. doi: 10.1051/dst/2009027.
   Web of Science ®Google Scholar
• Eduardo, L., T. Birgit, B. J. Julio, M. Antonio, M. Gosia, B. Luis, C. J. Juan, G. María, F. Juristo, and F. Susan. 2006. Absorption of calcium from milks enriched with fructo-oligosaccharides, caseinophosphopeptides, tricalcium phosphate, and milk solids. The American Journal of Clinical Nutrition 83 (2):310–6. doi: 10.1093/ajcn/83.2.310. doi:.
   PubMed Web of Science ®Google Scholar
• Ellegård, K. H., C. Gammelgård-Larsen, E. S. Sørensen, and S. Fedosov. 1999. Process scale chromatographic isolation, characterization and identification of tryptic bioactive casein phosphopeptides. International Dairy Journal 9 (9):639–52. doi: 10.1016/S0958-6946(99)00135-1.
   Web of Science ®Google Scholar
• Erba, D., S. Ciappellano, and G. Testolin. 2002. Effect of the ratio of casein phosphopeptides to calcium (w/w) on passive calcium transport in the distal small intestine of rats. Nutrition 18 (9):743–6. doi: 10.1016/S0899-9007(02)00829-8.
   PubMed Web of Science ®Google Scholar
• Farrell Jr., H. M., P. X. Qi, E. D. Wickham, and J. J. Unruh. 2002. Secondary structural studies of bovine caseins: Structure and temperature dependence of β-Casein phosphopeptide (1-25) as analyzed by circular dichroism, FTIR spectroscopy, and analytical ultracentrifugation. Journal of Protein Chemistry 21 (5):307–21. doi: 10.1023/A:1019992900455.
   PubMedGoogle Scholar
• Ferraretto, A., C. Gravaghi, A. Fiorilli, and G. Tettamanti. 2003. Casein-derived bioactive phosphopeptides: Role of phosphorylation and primary structure in promoting calcium uptake by HT-29 tumor cells. FEBS Letters 551 (1-3):92–8. doi: 10.1016/S0014-5793(03)00741-5.
   PubMed Web of Science ®Google Scholar
• Ferraretto, A., A. Signorile, C. Gravaghi, A. Fiorilli, and G. Tettamanti. 2001. Casein phosphopeptides influence calcium uptake by cultured human intestinal HT-29 tumor cells. The Journal of Nutrition 131 (6):1655–61. doi: 10.1093/jn/131.6.1655.
   PubMed Web of Science ®Google Scholar
• FitzGerald, R. J. 1998. Potential uses of caseinophosphopeptides. International Dairy Journal 8 (5–6):451–7. doi: 10.1016/S0958-6946(98)00068-5.
   Web of Science ®Google Scholar
• Fujita, H., H. Chiba, H. Yokozaki, N. Sakai, K. Sugimoto, T. Wada, T. Kojima, T. Yamashita, and N. Sawada. 2006. Differential expression and subcellular localization of claudin-7, -8, -12, -13, and -15 along the mouse intestine. The Journal of Histochemistry and Cytochemistry 54 (8):933–44. doi: 10.1369/jhc.6A6944.2006.
   PubMed Web of Science ®Google Scholar
• Gao, A., S. Dong, X. Wang, S. Li, and Y. Chen. 2018. Preparation, characterization and calcium release evaluation in vitro of casein phosphopeptides-soluble dietary fibers copolymers as calcium delivery system. Food Chemistry 245:262–9. doi: 10.1016/j.foodchem.2017.10.036.
   PubMed Web of Science ®Google Scholar
• García-Nebot, M. J., A. Alegría, R. Barberá, M. Del Mar Contreras, and A. Alegría. 2010. Milk versus caseinophosphopeptides added to fruit beverage: Resistance and release from simulated gastrointestinal digestion. Peptides 31 (4):555–61. doi: 10.1016/j.peptides.2009.12.021.
   PubMed Web of Science ®Google Scholar
• Granata, D., F. Baftizadeh, J. Habchi, C. Galvagnion, A. De Simone, C. Camilloni, A. Laio, and M. Vendruscolo. 2015. The inverted free energy landscape of an intrinsically disordered peptide by simulations and experiments. Scientific Reports 5:15449. doi: 10.1038/srep15449.
   PubMed Web of Science ®Google Scholar
• Gravaghi, C., F. E. Del, L. Cantu’, E. Donetti, M. Bedoni, A. Fiorilli, G. Tettamanti, and A. Ferraretto. 2007. Casein phosphopeptide promotion of calcium uptake in HT-29 cells - relationship between biological activity and supramolecular structure. The FEBS Journal 274 (19):4999–5011. doi: 10.1111/j.1742-4658.2007.06015.x.
   PubMed Web of Science ®Google Scholar
• Guéguen, L, and A. Pointillart. 2000. The bioavailability of dietary calcium. Journal of the American College of Nutrition 19 (2 Suppl):119S–36S. doi: 10.1080/07315724.2000.10718083.
   PubMed Web of Science ®Google Scholar
• Gumbiner, B. M. 1996. Cell adhesion: The molecular basis of tissue architecture and morphogenesis. Cell 84 (3):345–57. doi: 10.1016/S0092-8674(00)81279-9.
   PubMed Web of Science ®Google Scholar
• Guo, L., P. A. Harnedy, B. Li, H. Hou, Z. Zhang, X. Zhao, and R. J. FitzGerald. 2014. Food protein-derived chelating peptides: Biofunctional ingredients for dietary mineral bioavailability enhancement. Trends in Food Science & Technology 37 (2):92–105. doi: 10.1016/j.tifs.2014.02.007.
   Web of Science ®Google Scholar
• Hansen, M. R. V. A., B. Sandstrom, M. Jensen, and S. S. Sorensen. 1997. Casein phosphopeptides improve zinc and calcium absorption from rice-based but not from whole-grain infant cereal. Journal of Pediatric Gastroenterology and Nutrition 24 (1):56–62. doi: 10.1097/00005176-199701000-00014.
   PubMed Web of Science ®Google Scholar
• Heaney, R. P., Y. Saito, and H. Orimo. 1994. Effect of caseinphosphopeptide on absorbability of co-ingested calcium in normal postmenopausal women. Journal of Bone and Mineral Metabolism 12 (1):77–81. doi: 10.1007/BF02383413.
   Google Scholar
• Hirayama, M., K. Toyota, G. Yamaguchi, H. Hidaka, and H. Naito. 2014. HPLC analysis of commercial casein phosphopeptides (CPP). Bioscience, Biotechnology, and Biochemistry 56 (7):1126–7. doi: 10.1271/bbb.56.1126.
   Google Scholar
• Hoenderop, J. G., B. Nilius, and R. J. Bindels. 2005. Calcium absorption across epithelia. Physiological Reviews 85 (1):373–422. doi: 10.1152/physrev.00003.2004.
   PubMed Web of Science ®Google Scholar
• Holt, C., E. S. Sørensen, and R. A. Clegg. 2010. Role of calcium phosphate nanoclusters in the control of calcification. The FEBS Journal 276 (8):2308–23. doi: 10.1111/j.1742-4658.2009.06958.x.
   Web of Science ®Google Scholar
• Holt, C., P. A. Timmins, N. Errington, and J. Leaver. 1998. A core-shell model of calcium phosphate nanoclusters stabilized by beta-casein phosphopeptides, derived from sedimentation equilibrium and small-angle X-ray and neutron-scattering measurements. European Journal of Biochemistry 252 (1):73–8. doi: 10.1046/j.1432-1327.1998.2520073.x.
   PubMedGoogle Scholar
• Holt, C., N. M. Wahlgren, and T. Drakenberg. 1996. Ability of a beta-casein phosphopeptide to modulate the precipitation of calcium phosphate by forming amorphous dicalcium phosphate nanoclusters. Biochemical Journal 314 (3):1035–9. doi: 10.1042/bj3141035.
   PubMedGoogle Scholar
• Hou, T., W. Liu, W. Shi, Z. Ma, and H. He. 2017. Desalted duck egg white peptides promote calcium uptake by counteracting the adverse effects of phytic acid. Food Chemistry 219:428–35. doi: 10.1016/j.foodchem.2016.09.166.
   PubMed Web of Science ®Google Scholar
• Hou, T., C. Wang, Z. Ma, W. Shi, L. Weiwei, and H. He. 2015. Desalted duck egg white peptides: Promotion of calcium uptake and structure characterization. Journal of Agricultural and Food Chemistry 63 (37):8170–6. doi: 10.1021/acs.jafc.5b03097.
   PubMed Web of Science ®Google Scholar
• Huq, N. L., K. J. Cross, and E. C. Reynolds. 2003. Nascent helix in the multiphosphorylated peptide αS2-casein(2-20). Journal of Peptide Science 9 (6):386–92. doi: 10.1002/psc.465.
   PubMed Web of Science ®Google Scholar
• Huq, N. L., K. J. Cross, and E. C. Reynolds. 2004. Molecular modelling of the multiphosphorylated casein phosphopeptide αS1-casein(59-79) based on NMR constraints. The Journal of Dairy Research 71 (1):28–32. doi: 10.1017/S0022029903006630.
   PubMed Web of Science ®Google Scholar
• Jiang, L., S. Li, N. Wang, S. Zhao, Y. Chen, and Y. Chen. 2021. Preparation of dextran-casein phosphopeptide conjugates, evaluation of its calcium binding capacity and digestion in vitro. Food Chemistry 352:129332. doi: 10.1016/j.foodchem.2021.129332.
   PubMed Web of Science ®Google Scholar
• Kasal, T., T. Honda, and S. Kiriyama. 2014. Caseinpbospbopeptides (CPP) in feces of rats fed casein diet. Bioscience, Biotechnology, and Biochemistry 56 (7):1150–1. doi: 10.1271/bbb.56.1150.
   Google Scholar
• Kawahara, T., K. Aruga, and H. Otani. 2005. Characterization of casein phosphopeptides from fermented milk products. Journal of Nutritional Science and Vitaminology 51 (5):377–81. doi: 10.3177/jnsv.51.377.
   PubMed Web of Science ®Google Scholar
• Korhonen, H., and A. Pihlanto. 2006. Bioactive peptides: Production and functionality. International Dairy Journal 16 (9):945–60. doi: 10.1016/j.idairyj.2005.10.012.
   Web of Science ®Google Scholar
• Kumosinski, T. F., M. E. Brown, and M. H. Farrell. 1993. Three-dimensional molecular modeling of bovine caseins: An energy-minimized β-Casein structure. Journal of Dairy Science 76 (4):931–45. doi: 10.3168/jds.S0022-0302(93)77420-2.
   PubMed Web of Science ®Google Scholar
• Lee, Y. S., T. Noguchi, and H. Naito. 1980. Phosphopeptides and soluble calcium in the small intestine of rats given a casein diet. The British Journal of Nutrition 43 (3):457–67. doi: 10.1079/BJN19800113.
   PubMed Web of Science ®Google Scholar
• Lee, Y. S., T. Noguchi, and H. Naito. 2007. Intestinal absorption of calcium in rats given diets containing casein or amino acid mixture: The role of casein phosphopeptides. The British Journal of Nutrition 49 (1):67–76. doi: 10.1079/BJN19830012.
   Google Scholar
• Li, J., X. Xie, Y. Wang, W. Yin, J. S. Antoun, M. Farella, and L. Mei. 2014. Long-term remineralizing effect of casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) on early caries lesions in vivo: A systematic review. Journal of Dentistry 42 (7):769–77. doi: 10.1016/j.jdent.2014.03.015.
   PubMed Web of Science ®Google Scholar
• Liao, W., H. Chen, W. Jin, Z. Yang, Y. Cao, and J. Miao. 2020. Three newlyisolated calcium-chelating peptides from Tilapia bone collagen hydrolysate enhance calcium absorption activity in intestinal Caco-2 cells. Journal of Agricultural and Food Chemistry 68 (7):2091–8. doi: 10.1021/acs.jafc.9b07602.
   PubMed Web of Science ®Google Scholar
• Liao, W., S. Liu, X. Liu, S. Duan, S. Xiao, Z. Yang, Y. Cao, and J. Miao. 2019. The purification, identification and bioactivity study of a novel calcium-binding peptide from casein hydrolysate. Food & Function 10 (12):7724–32. doi: 10.1039/c9fo01383k.
   PubMed Web of Science ®Google Scholar
• Lin, F.-Y., W.-Y. Chen, and S.-Y. Huang. 2000. Selective separation of caseinophosphopeptides through immobilized metal ion affinity chromatography: effects of pH values, salt concentrations and degree of phosphorylation. Bioprocess Engineering 23 (5):467–71. doi:10.1007/s004499900178.
   Google Scholar
• Lindorff-Larsen, K., P. Maragakis, S. Piana, M. P. Eastwood, R. O. Dror, and D. E. Shaw. 2012. Systematic validation of protein force fields against experimental data. PloS One 7 (2):e32131. doi: 10.1371/journal.pone.0032131.
   PubMed Web of Science ®Google Scholar
• Liu, W., J. Lu, F. Gao, R. Gu, F. Lin, D. Ren, and M. Cai. 2015. Preparation, characterization and identification of calcium-chelating Atlantic salmon (Salmo salar L.) ossein oligopeptides. European Food Research and Technology 241 (6):851–60. doi: 10.1007/s00217-015-2510-2.
   Web of Science ®Google Scholar
• Liu, H., Y. Lv, J. Xu, and S. Guo. 2017. Interaction mode of calcium-binding peptides and Caco-2 cell membrane. Food Research International 102:225–33. doi: 10.1016/j.foodres.2017.09.077.
   PubMed Web of Science ®Google Scholar
• Liu, G., S. Sun, B. Guo, B. Miao, Z. Luo, Z. Xia, D. Ying, F. Liu, B. Guo, J. Tang, et al. 2018. Bioactive peptide isolated from casein phosphopeptides promotes calcium uptake in vitro and in vivo. Food & Function 9 (4):2251–60. doi: 10.1039/C7FO01709J.
   PubMed Web of Science ®Google Scholar
• Liu, F. R., L. Wang, R. Wang, and Z. X. Chen. 2013. Calcium-binding capacity of wheat germ protein hydrolysate and characterization of Peptide-calcium complex. Journal of Agricultural and Food Chemistry 61 (31):7537–44. doi: 10.1021/jf401868z.
   PubMed Web of Science ®Google Scholar
• Lu, Y., R. Nie, F. Li, and Z. Liu. 2016. Effects of calcium-binding peptide from tilapia scale protein hydrolysates on calcium absorption in Caco-2 cells. Journal of Aquatic Food Product Technology 25 (8):1213–20. doi: 10.1080/10498850.2015.1051258.
   Web of Science ®Google Scholar
• Luo, M., J. Xiao, S. Sun, F. Cui, G. Liu, W. Li, Y. Li, and Y. Cao. 2020. Deciphering calcium-binding behaviors of casein phosphopeptides by experimental approaches and molecular simulation. Food & Function 11 (6):5284–92. doi: 10.1039/D0FO00844C.
   PubMed Web of Science ®Google Scholar
• Malin, E. L., M. H. Alaimo, E. M. Brown, J. M. Aramini, M. W. Germann, H. M. Farrell Jr., P. L. H. McSweeney, and P. F. Fox. 2001. Solution structures of casein peptides: NMR, FTIR, CD, and molecular modeling studies of αs1-Casein, 1–23. Journal of Protein Chemistry 20 (5):391–404. doi: 10.1023/A:1012232804665.
   PubMedGoogle Scholar
• Matsui, T., H. Yano, T. Awano, T. Harumoto, and Y. Saito. 1994. The influences of casein phosphopeptides on metabolism of ectopic bone induced by decalcified bone matrix implantation in rats. Journal of Nutritional Science and Vitaminology 40 (2):137–45. doi: 10.3177/jnsv.40.137.
   PubMed Web of Science ®Google Scholar
• McDonagh, D., and R. J. FitzGerald. 1998. Production of caseinophosphopeptides (CPPs) from sodium caseinate using a range of commercial protease preparations. International Dairy Journal 8 (1):39–45. doi: 10.1016/S0958-6946(98)00019-3.
   Web of Science ®Google Scholar
• Meisel, H., H. Bernard, S. Fairweather-Tait, R. J. FitzGerald, R. Hartmann, C. N. Lane, D. McDonagh, B. Teucher, and J. M. Wal. 2003. Detection of caseinophosphopeptides in the distal ileostomy fluid of human subjects. The British Journal of Nutrition 89 (3):351–9. doi: 10.1079/BJN2002803.
   PubMed Web of Science ®Google Scholar
• Meisel, H., and H. Frister. 1988. Chemical characterization of a caseinophosphopeptide isolated from in vivo digests of a casein diet. Biological Chemistry Hoppe-Seyler 369 (12):1275–80. doi: 10.1515/bchm3.1988.369.2.1275.
   PubMed Web of Science ®Google Scholar
• Mellander, O. 1950. The physiological importance of the casein phosphopeptide calcium salts. II. Peroral calcium dosage of infants. Acta Societatis Medicorum Upsaliensis 55 (5–6):247–55. PMID: 15443982.
   PubMedGoogle Scholar
• Miquel, E., A. Alegría, R. Barberá, and R. Farré. 2006a. Casein phosphopeptides released by simulated gastrointestinal digestion of infant formulas and their potential role in mineral binding. International Dairy Journal 16 (9):992–1000. doi: 10.1016/j.idairyj.2005.10.010.
   Web of Science ®Google Scholar
• Miquel, E., J. Ángel Gómez, A. Alegría, R. Barberá, R. Farré, and I. Recio. 2006b. Identification of casein phosphopeptides after simulated gastrointestinal digestion by tandem mass spectrometry. European Food Research and Technology 222 (1-2):48–53. doi: 10.1007/s00217-005-0023-0.
   Web of Science ®Google Scholar
• Miquel, E., J. A. Gómez, A. Alegría, R. Barberá, R. Farré, and I. Recio. 2006c. Identification of casein phosphopeptides in β-casein and commercial hydrolysed casein by mass spectrometry. Food Science and Technology International 12 (5):379–84. doi: 10.1177/1082013206070434.
   Web of Science ®Google Scholar
• Miquel, E., and R. Farré. 2007. Effects and future trends of casein phosphopeptides on zinc bioavailability. Trends in Food Science & Technology 18 (3):139–43. doi: 10.1016/j.tifs.2006.11.004.
   Web of Science ®Google Scholar
• Miquel, E., J. A. Gomez, A. Alegria, R. Barbera, R. Farre, and I. Recio. 2005. Identification of casein phosphopeptides released after simulated digestion of milk-based infant formulas. Journal of Agricultural and Food Chemistry 53 (9):3426–33. doi: 10.1021/jf0482111.
   PubMed Web of Science ®Google Scholar
• Morgan, M. V., G. G. Adams, D. L. Bailey, C. E. Tsao, S. L. Fischman, and E. C. Reynolds. 2008. The anticariogenic effect of sugar-free gum containing CPP-ACP nanocomplexes on approximal caries determined using digital bitewing radiography. Caries Research 42 (3):171–84. doi: 10.1159/000128561.
   PubMed Web of Science ®Google Scholar
• Mykkanen, H. M., and R. H. Wasserman. 1980. Enhanced absorption of calcium by casein phosphopeptides in rachitic and normal chicks. The Journal of Nutrition 110 (11):2141–8. doi: 10.1093/jn/110.11.2141.
   PubMed Web of Science ®Google Scholar
• Naito, H., and H. Suzuki. 1974. Further Evidence for the Formation in vivo of Phosphopeptide in the Intestinal Lumen from Dietary β-Casein. Agricultural and Biological Chemistry 38 (8):1543–5. doi: 10.1080/00021369.1974.10861372.
   Web of Science ®Google Scholar
• Naqvi, M. A., S. Rauscher, R. Pomès, and D. Rousseau. 2014. The conformational ensemble of the β-Casein phosphopeptide reveals two independent intrinsically disordered segments. Biochemistry 53 (40):6402–8. doi: 10.1021/bi500107u.
   PubMed Web of Science ®Google Scholar
• Naqvi, M. A., J. Singh, E. Han, K. Farshad, and D. Rousseau. 2016. Purification and identification of β-casein phosphopeptide (1-25). Journal of Dairy Science 99 (10):7803–8. doi: 10.3168/jds.2016-11010.
   PubMed Web of Science ®Google Scholar
• Narva, M., M. Kärkkäinen, T. Poussa, C. Lamberg-Allardt, and R. Korpela. 2003. Caseinphosphopeptides in milk and fermented milk do not affect calcium metabolism acutely in postmenopausal women. Journal of the American College of Nutrition 22 (1):88–93. doi: 10.1080/07315724.2003.10719280.
   PubMed Web of Science ®Google Scholar
• Nongonierma, A. B., and R. J. FitzGerald. 2015. The scientific evidence for the role of milk protein-derived bioactive peptides in humans: A review. Journal of Functional Foods 17:640–56. doi: 10.1016/j.jff.2015.06.021.
   Web of Science ®Google Scholar
• Olumee-Shabon, Z., and J. L. Boehmer. 2013. Detection of casein phosphopeptides in goat milk. Journal of Proteome Research 12 (6):3034–41. doi: 10.1021/pr3010666.
   PubMed Web of Science ®Google Scholar
• Ono, T., T. Ohotawa, and Y. Takagi. 1994. Complexes of casein phosphopeptide and calcium phosphate prepared from casein micelles by tryptic digestion. Bioscience, Biotechnology, and Biochemistry 58 (8):1376–80. doi: 10.1271/bbb.58.1376.
   PubMed Web of Science ®Google Scholar
• Ono, T., Y. Takagi, and I. Kunishi. 1998. Casein phosphopeptides from casein micelles by successive digestion with pepsin and trypsin. Bioscience, Biotechnology, and Biochemistry 62 (1):16–21. doi: 10.1271/bbb.62.16.
   PubMed Web of Science ®Google Scholar
• Park, O., and J. C. Allen. 1998. Preparation of phosphopeptides derived from αs-casein and β-casein using immobilized glutamic acid-specific endopeptidase and characterization of their calcium binding. Journal of Dairy Science 81 (11):2858–65. doi: 10.3168/jds.S0022-0302(98)75845-X.
   PubMed Web of Science ®Google Scholar
• Parkinson, G. B., and P. H. Cransberg. 2004. Effect of casein phosphopeptide and 25-hydroxycholecalciferol on tibial dyschondroplasia in growing broiler chickens. British Poultry Science 45 (6):802–6. doi: 10.1080/00071660400012733.
   PubMed Web of Science ®Google Scholar
• Park, O., H. E. Swaisgood, and J. C. Allen. 1998. Calcium binding of phosphopeptides derived from hydrolysis of a αs-casein or β-casein using immobilized trypsin. Journal of Dairy Science 81 (11):2850–7. doi: 10.3168/jds.S0022-0302(98)75844-8.
   PubMed Web of Science ®Google Scholar
• Peng, Z., H. Hou, K. Zhang, and B. Li. 2017. Effect of calcium-binding peptide from Pacific cod (Gadus macrocephalus) bone on calcium bioavailability in rats. Food Chemistry 221:373–8. doi: 10.1016/j.foodchem.2016.10.078.
   PubMed Web of Science ®Google Scholar
• Perego, S., S. Cosentino, A. Fiorilli, G. Tettamanti, and A. Ferraretto. 2012. Casein phosphopeptides modulate proliferation and apoptosis in HT-29 cell line through their interaction with voltage-operated L-type calcium channels. The Journal of Nutritional Biochemistry 23 (7):808–16. doi: 10.1016/j.jnutbio.2011.04.004.
   PubMed Web of Science ®Google Scholar
• Perego, S., A. Zabeo, E. Marasco, P. Giussani, A. Fiorilli, G. Tettamanti, and A. Ferraretto. 2013. Casein phosphopeptides modulate calcium uptake and apoptosis in Caco-2 cells through their interaction with the TRPV6 calcium channel. Journal of Functional Foods 5 (2):847–57. doi: 10.1016/j.jff.2013.01.032.
   Web of Science ®Google Scholar
• Prakash, D., and A. J. Lakshmi. 2015. Preparation of caseinophosphopeptides and assessing their efficacy in enhancing the bioaccessibility of iron and zinc. Journal of Food Science and Technology 52 (11):7493–9. doi: 10.1007/s13197-015-1864-6.
   Web of Science ®Google Scholar
• Recio, R. T., N. P. Guerra, A. Torrado, and L. H. Skibsted. 2019. Interaction between calcium and casein hydrolysates: Stoichiometry, binding constant, binding sites and thermal stability of casein phosphopeptide complexes. International Dairy Journal 88:25–33. doi: 10.1016/j.idairyj.2018.08.009.
   Web of Science ®Google Scholar
• Reynolds, E. C., P. F. Riley, and N. J. Adamson. 1994. A selective precipitation purification procedure for multiple phosphoseryl-containing peptides and methods for their identification. Analytical Biochemistry 217 (2):277–84. doi: 10.1006/abio.1994.1119.
   PubMed Web of Science ®Google Scholar
• Ryuichiro, S., T. Noguchi, and H. Naito. 1983. The necessity for the phosphate portion of casein molecules to enhance Ca absorption from the small intestine. Agricultural and Biological Chemistry 47 (10):2415–7. doi: 10.1080/00021369.1983.10865972.
   Google Scholar
• Saini, P., B. Mann, R. Kumar, R. Sharma, R. R. Singh, and A. Chatterjee. 2014. Process optimisation for preparation of caseinophosphopeptides from buffalo milk casein and their characterisation. The Journal of Dairy Research 81 (3):364–71. doi: 10.1017/S0022029914000296.
   PubMed Web of Science ®Google Scholar
• Saito, Y., Y. S. Lee, and S. Kimura. 1998. Minimum effective dose of casein phosphopeptides (CPP) for enhancement of calcium absorption in growing rats. International Journal for Vitamin and Nutrition Research 68 (5):335–40. PMID: 9789766.
   PubMed Web of Science ®Google Scholar
• Sanchón, J., S. Fernández-Tomé, B. Miralles, B. Hernández-Ledesma, D. Tomé, C. Gaudichon, and I. Recio. 2018. Protein degradation and peptide release from milk proteins in human jejunum. Comparison with in vitro gastrointestinal simulation. Food Chemistry 239:486–94. doi: 10.1016/j.foodchem.2017.06.134.
   PubMed Web of Science ®Google Scholar
• Sato, R., T. Noguchi, and H. Naito. 1986. Casein phosphopeptide (cpp) enhances calcium absorption form the ligated segment of rat small intestine. Journal of Nutritional Science and Vitaminology 32 (1):67–76. doi: 10.3177/jnsv.32.67.
   PubMed Web of Science ®Google Scholar
• Silva, R. A., V. S. Bezerra, M. C. Pimentel, A. L. Porto, M. T. Cavalcanti, and J. L. Filho. 2016. Proteomic and peptidomic profiling of Brazilian artisanal ‘Coalho’ cheese. Journal of the Science of Food and Agriculture 96 (13):4337–44. doi: 10.1002/jsfa.7640.
   PubMed Web of Science ®Google Scholar
• Stanley, N., S. Esteban-Martín, and G. D. Fabritiis. 2014. Kinetic modulation of a disordered protein domain by phosphorylation. Nature Communications 5:5272. doi: 10.1038/ncomms6272.
   PubMed Web of Science ®Google Scholar
• Straub, D. A. 2007. Calcium supplementation in clinical practice: A review of forms, doses, and indications. Nutrition in Clinical Practice 22 (3):286–96. doi: 10.1177/0115426507022003286.
   PubMed Web of Science ®Google Scholar
• Sun, N., S. Hu, D. Wang, P. Jiang, S. Zhang, and S. Lin. 2022. Calcium delivery systems assembled using antarctic krill derived heptapeptides: Exploration of the assembly mechanism, in vitro digestion profile, and calcium absorption behavior. Journal of Agricultural and Food Chemistry 70 (6):2018–28. doi: 10.1021/acs.jafc.1c06951.
   PubMed Web of Science ®Google Scholar
• Sun, S., F. Liu, G. Liu, J. Miao, H. Xiao, J. Xiao, Z. Qiu, Z. Luo, J. Tang, and Y. Cao. 2018. Effects of casein phosphopeptides on calcium absorption and metabolism bioactivity in vitro and in vivo. Food & Function 9 (10):5220–9. doi: 10.1039/C8FO00401C.
   PubMed Web of Science ®Google Scholar
• Sun, N., H. Wu, M. Du, Y. Tang, H. Liu, Y. Fu, and B. Zhu. 2016. Food protein-derived calcium chelating peptides: A review. Trends in Food Science & Technology 58:140–8. doi: 10.1016/j.tifs.2016.10.004.
   Web of Science ®Google Scholar
• Suzuki, Y., C. P. Landowski, and M. A. Hediger. 2008. Mechanisms and regulation of epithelial Ca2+ absorption in health and disease. Annual Review of Physiology 70 (1):257–71. doi: 10.1146/annurev.physiol.69.031905.161003.
   PubMedGoogle Scholar
• Tang, N., and L. H. Skibsted. 2016. Calcium binding to amino acids and small glycine peptides in aqueous solution: Toward peptide design for better calcium bioavailability. Journal of Agricultural and Food Chemistry 64 (21):4376–89. doi: 10.1021/acs.jafc.6b01534.
   PubMed Web of Science ®Google Scholar
• Teucher, B., G. Majsak-Newman, J. R. Dainty, D. Mcdonagh, R. J. Fitzgerald, and S. J. Fairweather-tait. 2006. Calcium absorption is not increased by caseinophosphopeptides. The American Journal of Clinical Nutrition 84 (1):162–6. doi: 10.1093/ajcn/84.1.162.
   PubMed Web of Science ®Google Scholar
• Tsuchita, H., T. Goto, T. Shimizu, Y. Yonehara, and T. Kuwata. 1996. Dietary casein phosphopeptides prevent bone loss in aged ovariectomized rats. The Journal of Nutrition 126 (1):86–93. doi: 10.1093/jn/126.1.86.
   PubMed Web of Science ®Google Scholar
• Tsuchita, H., I. Sekiguchi, T. Kuwata, C. Igarashi, and I. Ezawa. 1993. The effect of casein phosphopeptides on calcium utilization in young ovariectomized rats. Zeitschrift Fur Ernahrungswissenschaft 32 (2):121–30. doi: 10.1007/BF01614755.
   PubMedGoogle Scholar
• Tsuchita, H., T. Suzuki, and T. Kuwata. 2001. The effect of casein phosphopeptides on calcium absorption from calcium-fortified milk in growing rats. British Journal of Nutrition 85 (1):5–10. doi: 10.1079/BJN2000206.
   PubMed Web of Science ®Google Scholar
• Tsuda, S., R. Niki, T. Kuwata, I. Tanaka, and K. Hikichi. 1991. 1H NMR study of casein phosphopeptide (1–25): Assignment and conformation. Magnetic Resonance in Chemistry 29 (11):1097–102. doi: 10.1002/mrc.1260291105.
   Web of Science ®Google Scholar
• Vavrusova, M., and L. H. Skibsted. 2014. Calcium nutrition. bioavailability and fortification. LWT - Food Science and Technology 59 (2):1198–204. doi: 10.1016/j.lwt.2014.04.034.
   Web of Science ®Google Scholar
• Wright, P. E., and H. J. Dyson. 2015. Intrinsically disordered proteins in cellular signalling and regulation. Nature Reviews. Molecular Cell Biology 16 (1):18–29. doi: 10.1038/nrm3920.
   PubMed Web of Science ®Google Scholar
• Xixi, C., Z. Lina, W. Shaoyun, and R. Pingfan. 2015. Fabrication and characterization of the nano-composite of whey protein hydrolysate chelated with calcium. Food & Function 6 (3):816–23. doi: 10.1039/c4fo00811a.
   PubMed Web of Science ®Google Scholar
• Yoshikawa, M., R. Sasaki, and H. Chiba. 1981. Effects of chemical phosphorylation of bovine casein components on the properties related to casein micelle formation. Agricultural and Biological Chemistry 45 (4):909–14. doi: 10.1271/bbb1961.45.909.
   Web of Science ®Google Scholar
• Yu, Y., Y. Qi, and Y. Jin. 2019. Milk digestion peptidomics: Tracking caseinophosphopeptides in simulated gastrointestinal digestion. Food Bioscience 28:143–50. doi: 10.1016/j.fbio.2019.01.019.
   Web of Science ®Google Scholar
• Yue, G. E., M. G. Roper, C. Balchunas, A. Pulsipher, J. J. Coon, J. Shabanowitz, D. F. Hunt, J. P. Landers, and J. P. Ferrance. 2006. Protein digestion and phosphopeptide enrichment on a glass microchip. Analytica Chimica Acta 564 (1):116–22. doi: 10.1016/j.aca.2005.11.003.
   PubMed Web of Science ®Google Scholar
• Zhang, K., J. Li, H. Hou, H. Zhang, and B. Li. 2019. Purification and characterization of a novel calcium-biding decapeptide from Pacific cod (Gadus Macrocephalus) bone: Molecular properties and calcium chelating modes. Journal of Functional Foods 52:670–9. doi: 10.1016/j.jff.2018.11.042.
   Web of Science ®Google Scholar
• Zhang, X., J. Ye, O. N. Jensen, and P. Roepstorff. 2007. Highly efficient phosphopeptide enrichment by calcium phosphate precipitation combined with subsequent IMAC enrichment*. Molecular & Cellular Proteomics 6 (11):2032–42. doi: 10.1074/mcp.M700278-MCP200.
   PubMed Web of Science ®Google Scholar
• Zhao, L., X. Cai, S. Huang, S. Wang, Y. Huang, J. Hong, and P. Rao. 2015. Isolation and identification of a whey protein-sourced calcium-binding tripeptide Tyr-Asp-Thr. International Dairy Journal 40:16–23. doi: 10.1016/j.idairyj.2014.08.013.
   Web of Science ®Google Scholar
• Zhao, L., S. Huang, X. Cai, J. Hong, and S. Wang. 2014. A specific peptide with calcium chelating capacity isolated from whey protein hydrolysate. Journal of Functional Foods 10:46–53. doi: 10.1016/j.jff.2014.05.013.
   Web of Science ®Google Scholar
• Zhao, L., Q. Huang, S. Huang, J. Lin, S. Wang, Y. Huang, J. Hong, and P. Rao. 2014. Novel peptide with a specific calcium-binding capacity from whey protein hydrolysate and the possible chelating mode. Journal of Agricultural and Food Chemistry 62 (42):10274–82. doi: 10.1021/jf502412f.
   PubMed Web of Science ®Google Scholar
• Zhao, W., G. Xu, R. Yang, and W. Katiyo. 2013. Preparation of casein phosphopeptides using a novel continuous process of combining an enzymatic membrane reactor with anion-exchange chromatography. Journal of Food Engineering 117 (1):105–12. doi: 10.1016/j.jfoodeng.2013.02.015.
   Web of Science ®Google Scholar
• Zheng, J., Q. Gao, C. Tang, G. Ge, M. Zhao, and W. Sun. 2020. Heteroprotein complex formation of soy protein isolate and lactoferrin: Thermodynamic formation mechanism and morphologic structure. Food Hydrocolloids. 100:105415. doi: 10.1016/j.foodhyd.2019.105415.
   Web of Science ®Google Scholar
• Zhu, Y. S., and R. J. FitzGerald. 2010. Direct nano HPLC-ESI-QTOF MS/MS analysis of tryptic caseinophosphopeptides. Food Chemistry 123 (3):753–9. doi: 10.1016/j.foodchem.2010.05.046.
   Web of Science ®Google Scholar
• Zhu, Y., and R. J. FitzGerald. 2012. Caseinophosphopeptide enrichment and identification. International Journal of Food Science & Technology 47 (10):2235–42. doi: 10.1111/j.1365-2621.2012.03094.x.
   Web of Science ®Google Scholar
• Zhu, S., X. Yu, J. You, T. Yin, Y. Lin, W. Chen, L. Dao, H. Du, R. Liu, S. Xiong, et al. 2021. Study of the thermodynamics and conformational changes of collagen molecules upon self-assembly. Food Hydrocolloids. 114:106576. doi: 10.1016/j.foodhyd.2020.106576.
   Web of Science ®Google Scholar
• Zidane, F., A. Mateos, C. Cakir-Kiefer, L. Miclo, S. Rahuel-Clermont, J. M. Girardet, and C. Corbier. 2012. Binding of divalent metal ions to 1-25 beta-caseinophosphopeptide: An isothermal titration calorimetry study. Food Chemistry 132 (1):391–8. doi: 10.1016/j.foodchem.2011.11.006.
   PubMed Web of Science ®Google Scholar
• Zong, H., L. Peng, S. Zhang, Y. Lin, and F. Feng. 2012. Effects of molecular structure on the calcium-binding properties of phosphopeptides. European Food Research and Technology 235 (5):811–6. doi: 10.1007/s00217-012-1809-5.
   Web of Science ®Google Scholar