# Proteomics Analysis in Dairy Products: Cheese, a Review
## 8 Bioactive Peptides
All the peptides were found to be generated by the hydrolysis of milk caseins (of different mammalian species, according to the type of milk used to produce the cheese), which typically occurred in specific regions of the proteins already known for the presence of bioactive amino acid sequences. Anithrombotic peptides are also present in milk. The mechanisms involved in blood and milk clotting are proportional, leading to the hypothesis that the C-terminal dodecapeptide of human fibrinogen \(\gamma\)-chain (residues 400-411) and the undecapeptide (residues 106-116) from bovine \(\kappa\)-CN are structurally and functionally quite similar. The casoplatelin is produced by hydrolysis of bovine k-casein with chymosin and shows antithrombotic properties [142]. This casein-derived peptide sequence affected platelet function and inhibited both the aggregation of ADP-activated platelets and the binding of human fibrinogen \(\lambda\)-chain to its receptor region on the platelets' surface [143]. A smaller \(\kappa\)-CN fragment (residues 106-110), casopiastrin, was obtained from trypsin hydrolysates and exhibited antithrombotic activity by inhibiting fibrinogen binding [143, 144]. A second segment of the trypsin \(\kappa\)-CN fragment, residues 103-111, inhibited platelet aggregation but did not affect fibrinogen binding to the platelet receptor [143, 145, 146]. Other studies concluded that bioactive peptides isolated from both casein and lactotransferrin had antithrombotic properties by affecting platelet function [147, 148]. Antithrombotic peptides have also been derived from \(\kappa\)-caseinoglycopeptides, that were isolated from several animal species. Bovine \(\kappa\)-caseinoglycopeptide, the C-terminal end of \(\kappa\)-CN (residues 106-169), inhibited von [PERSON] factor-dependent platelet aggregation [149]. Two antithrombotic peptides, derived from human and bovine \(\kappa\)-caseinoglycopeptides, have been identified in the plasma of 5d-old neonatals after breast-feeding and ingestion of cow's milk-based formula, respectively [150]. The C-terminal residues (106-171) of sheep \(\kappa\)-casein, or \(\kappa\)-caseinoglycopeptide, decreased thrombin- and collagen-induced platelet aggregation in a dose dependent manner [151]. Finally, thrombin-induced platelet aggregation was inhibited by pepsin digests of sheep and human lactoferrin [152]. Casein phosphopeptides (CPP) are the result of trypsin action in\(\alpha\)s1-, \(\alpha\)s2-, and \(\beta\)-CN [153]. CPP are stable molecules even after gastrointestinal digestion and create a high soluble complex with calcium phosphate [154]. Animals fed with casein diet displayed elevated capacity to absorb calcium through distal small intestines compared to animals fed with soy-based diet [155; 156; 157]. Calcium physiological is absorbed through passive transport system and this is the way to supplement the human/animal organism with the calcium required for calcification [158]. Caseinophosphopeptides inhibit caries lesions through recalcification of the dental enamel, so their application in the treatment of dental diseases has been proposed [159]. Buffalo (_Bubalus bubalis_) milk contains a lot of bioactive peptides and they have a significant role preventing various disorders [160; 161; 162; 163]. Bioactive peptides with antioxidant properties, regulation of oxidative stress in intestinal epithelial cells and erythrocytes, have been isolated from buffalo milk-derived products [164; 165]. Among these, MBCP, a peptide isolated after in vitro digestion of Mozzarella di Bufala Campana DOP, has shown good stability to brush border exopeptidases and a high bioavailability [166]. In a study conducted by [PERSON] et al. [165], the therapeutic potential of MBCP in inflammatory bowel disease (IBD) was discussed after submitting Caco-2 cell, which resembles colonic enterocytes [167], in in vitro digestion conditions. In mammals, enterocytes are renewed continuously every 4-8 days through an organized cycle involving proliferation, differentiation and programmed cell death.