Sheep κ-casein peptides inhibit platelet aggregation

• Published in: Biochimica et biophysica acta 1995-06, Vol.1244 (2), p.411-417
• Main Authors: Qian, Zu-Yuan, Jollès, Pierre, Migliore-Samour, Danièle, Schoentgen, Françoise, Fiat, Anne-Marie
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Animals; Blood; Caseins - administration & dosage; Caseins - chemistry; Caseins - pharmacology; Chromatography, High Pressure Liquid; Collagen - pharmacology; Dose-Response Relationship, Drug; Drug Stability; Electrophoresis, Polyacrylamide Gel; Fibrinogen - chemistry; Guinea Pigs; Humans; Milk; Molecular Sequence Data; Peptide Fragments - chemistry; Peptide Fragments - isolation & purification; Peptide Fragments - pharmacology; Platelet aggregation; Platelet Aggregation - drug effects; Platelet Aggregation Inhibitors - pharmacology; Protein Structure, Secondary; Sheep; Thrombin - pharmacology; Trypsin - metabolism; κ-Casein
• ISSN: 0304-4165; 0006-3002; 1872-8006
• DOI: 10.1016/0304-4165(95)00047-F

The C-terminal part (residues 106–171) of sheep κ-casein, called caseinoglycopeptide (CGP), inhibits thrombin- and collagen-induced platelet aggregation in a dose-dependent manner (mean inhibitory concentration (IC 50) 215 μM and 100 μM, respectively). An enzymatic hydrolysate of CGP was fractionated by reverse phase high performance liquid chromatography: three peptides KDQDK (residues 112–116), TAQVTSTEV (residues 163–171) and QVTSTEV (residues 165–171) completely inhibited thrombin-induced platelet aggregation. CGP at a concentration near its IC 50 had a very long life when incubated in human or guinea-pig plasma. An ex vivo experiment showed that 17% of CGP was found 60 min after its i.v. bolus injection in guinea-pig. By hydrophobic cluster analysis, human fibrinogen and sheep κ-casein peptides, inhibitors of platelet aggregation, were compared and we observed similarities for their C-terminal parts and for their short peptides (RGDF and KDQDK).