Inhibition of platelet activation by peptide analogs of the beta(3)-intracellular domain of platelet integrin alpha(IIb)beta(3) conjugated to the cell-penetrating peptide Tat(48-60).

Activation of the platelet integrin-receptor αIIbβ3 is the final pathway of platelet aggregation, regardless of the initiating stimulus. Many studies suggest that there are several cytoplasmic proteins such as talin and β3-endonexin that bind to N744PLY747 and N756ITY759 motif of the β3 cytoplasmic tail and play the major role in the receptor activation. In this study, we investigated the role of the membrane distal region of human β3 cytoplasmic tail and specifically the N743NPLYKEA750 and T755NITYRGT762 sequence that contains an NXXY motif, in platelet aggregation, secretion, αIIbβ3 activation (PAC-1 binding) and fibrinogen binding. We synthesized two peptides corresponding to the above sequences as well as their conjugates with the Tat(48–60) cell-penetrating peptide. The capability of conjugates to penetrate the platelet membrane was investigated with confocal laser scanning microscopy using carboxyfluorescein (CF)-labeled peptides. Our results showed that the conjugated with the Tat(48–60) sequence p...