Sheep kappa-casein peptides inhibit platelet aggregation.
The C-terminal part (residues 106-171) of sheep kappa-casein, called caseinoglycopeptide (CGP), inhibits thrombin- and collagen-induced platelet aggregation in a dose-dependent manner (mean inhibitory concentration (IC50) 215 microM and 100 microM, 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 IC50 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 kappa-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).
Qian
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Laboratoire des Protéines, CNRS URA 1188, University of Paris V, France.
Jollès
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Migliore-Samour
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Schoentgen
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Fiat
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AM
D000595:Amino Acid Sequence; D000818:Animals; D001769:Blood; D002364:Caseins / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D003094:Collagen / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004355:Drug Stability; D004591:Electrophoresis, Polyacrylamide Gel; D005340:Fibrinogen / Q000737:chemistry; D006168:Guinea Pigs; D006801:Humans; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D017433:Protein Structure, Secondary; D012756:Sheep; D013917:Thrombin / Q000494:pharmacology; D014357:Trypsin / Q000378:metabolism
D002364:Caseins; D010446:Peptide Fragments; D010975:Platelet Aggregation Inhibitors; D005340:Fibrinogen; D003094:Collagen; D014357:Trypsin; D013917:Thrombin