Bal dit Sollier C, Drouet L, Pignaud G, Chevallier C, Caen J, Fiat A M, Izquierdo C, Jolles P
Institut des Vaisseaux et du Sang, Hopital Lariboisiere, Paris, France.
Thromb Res. 1996 Feb 15;81(4):427-37. doi: 10.1016/0049-3848(96)00015-1.
An undecapeptide (residues 106-116 of cow kappa-casein) is known to inhibit human platelet aggregation and fibrinogen binding through inhibition of the interaction between the fibrinogen gamma-chain C-terminus and alphaIIbbeta3. This was due to structural homologies with the fibrinogen gamma-chain C-terminal dodecapeptide. We have therefore compared in this work the in vitro anti-aggregating activity of kappa-casein split peptides and their in vivo potential antithrombotic activity in a model of arterial thrombosis triggered by laser-induced intimal injury in the guinea-pig. Caseinoglycopeptide (residues 106-169), the undecapeptide (residues 106-116) and the pentapeptide KNQDK (residues 112-116) from cow kappa-casein, were anti-aggregating peptides and exerted a significant antithrombotic activity in the guinea-pig. Caseinoglycopeptides from three species (cow, ewe and human) were also antithrombotic and the most potent being the human one. The antithrombotic activity was achieved in vivo for doses less than the one suspected from in vitro data and for which, ex vivo platelet aggregation was not decreased. In conclusion, the relative involvement of the fibrinogen gamma-chain C-terminal dodecapeptide could be much more important in in vivo thrombosis process than in in vitro platelet aggregation. Its specificity and activity in vivo unveiled an interesting potential way for inhibition of arterial thrombosis if alternative molecular presentation (i.e. peptidomimetics) and alternative route (i.e. per os) can be developed.
已知一种十一肽（牛κ-酪蛋白的106 - 116位残基）可通过抑制纤维蛋白原γ链C末端与αIIbβ3之间的相互作用来抑制人血小板聚集和纤维蛋白原结合。这是由于其与纤维蛋白原γ链C末端十二肽存在结构同源性。因此，在本研究中，我们比较了κ-酪蛋白裂解肽的体外抗聚集活性及其在豚鼠激光诱导内膜损伤引发的动脉血栓形成模型中的体内潜在抗血栓活性。酪蛋白糖肽（106 - 169位残基）、十一肽（106 - 116位残基）和来自牛κ-酪蛋白的五肽KNQDK（112 - 116位残基）均为抗聚集肽，并在豚鼠中发挥了显著的抗血栓活性。来自三种物种（牛、羊和人）的酪蛋白糖肽也具有抗血栓作用，其中人源酪蛋白糖肽的活性最强。体内抗血栓活性是在剂量低于体外数据推测的剂量时实现的，并且在此剂量下，体外血小板聚集并未降低。总之，纤维蛋白原γ链C末端十二肽在体内血栓形成过程中的相对作用可能比在体外血小板聚集中更为重要。如果能够开发出替代的分子呈现方式（即拟肽）和替代途径（即口服），其在体内的特异性和活性揭示了一种抑制动脉血栓形成的有趣潜在方法。
