Cb. Sollier et al., EFFECT OF KAPPA-CASEIN SPLIT PEPTIDES ON PLATELET-AGGREGATION AND ON THROMBUS FORMATION IN THE GUINEA-PIG, Thrombosis research, 81(4), 1996, pp. 427-437
An undecapeptide (residues 106-116 of cow K-casein) is known to inhibi
t human platelet aggregation and fibrinogen binding through inhibition
of the interaction between the fibrinogen gamma-chain C-terminus and
alpha(IIb)beta(3). This was due to structural homologies with the fibr
inogen gamma-chain C-terminal dodecapeptide. We have therefore compare
d 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 inju
ry in the guinea-pig. Caseinoglycopeptide (residues 106-169), the unde
capeptide (residues 106-116) and the pentapeptide KNQDK (residues 112-
116) from cow K-casein, were anti-aggregating peptides and exerted a s
ignificant antithrombotic activity in the guinea-pig. Caseinoglycopept
ides from three species (cow, ewe and human) were also antithrombotic
and the most potent being the human one. The antithrombotic activity w
as achieved in vivo for doses less than the one suspected from in vitr
o 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 throm
bosis process than in in vitro platelet aggregation. Its specificity a
nd activity in vivo unveiled an interesting potential way for inhibiti
on of arterial thrombosis if alternative molecular presentation (i.e.
peptidomimetics) and alternative route (i.e. per os) can be developed.