TAILIEUCHUNG - Báo cáo khóa học: Effect of synthetic peptides corresponding to residues 313–332 of the aIIb subunit on platelet activation and fibrinogen binding to aIIbb3

The platelet integrin receptoraIIbb3 plays a critical role in thrombosis and haemostasis by mediating interactions between platelets and several ligands but primarily fibrin-ogen. It has been shown previously that the YMESRADR KLAEVGRVYLFL (313–332) sequence of theaIIb subunit plays an important role in platelet activation, fibrinogen binding andaIIbb3 -mediated outside-in signalling. Further-more, we recently showed that the 20-residue peptide (20-mer) aIIb 313–332, is a potent inhibitor of platelet aggregationandfibrinogenbindingtoaIIbb3, interactingwith fibrinogen rather than the receptor | Eur. J. Biochem. 271 855-862 2004 FEBS 2004 doi Effect of synthetic peptides corresponding to residues 313-332 of the aIIb subunit on platelet activation and fibrinogen binding to aIIbp3 John V Mitsios1. Afroditi P. Tambaki1. Morfis Abatzis1. Nikolaos Biris1. Maria Sakarellos-Daitsiotis1 . . Constantinos Sakarellos1. Ketty Soteriadou3 John Goudevenos2 Moses Elisaf2 Demokritos Tsoukatos1 Vassilios Tsikaris1 and Alexandros D. Tselepis1 -Department of Chemistry and 2Medical School University of loannina 3Department of Biochemistry Hellenic Pasteur Institute Vasilisis Sofias Athens Greece The platelet integrin receptor aIIbp3 plays a critical role in thrombosis and haemostasis by mediating interactions between platelets and several ligands but primarily fibrinogen. It has been shown previously that the YMESRADR KLAEVGRVYLFL 3-3-332 sequence of the aIIb subunit plays an important role in platelet activation fibrinogen binding and aIIbp3-mediated outside-in signalling. Furthermore we recently showed that the 20-residue peptide 20-mer aIIb 3-3-332 is a potent inhibitor of platelet aggregation and fibrinogen binding to aIIbp3 interacting with fibrinogen rather than the receptor. In an effort to determine the sequence and the minimum length required for the biological activity of the above 20-mer we synthesized seven octapeptides each overlapping by six residues covering the entire sequence and studied their effect on platelet activation as well as fibrinogen binding to activated platelets. We show for the first time that octapeptides containing the RAD sequence are capable of inhibiting platelet aggregation and secretion as well as fibrinogen binding to the activated aIIbp3 possibly interacting with the ligand rather than the receptor. This suggests that the RAD sequence common to all the inhibitory peptides is critical for their biological activity. However the presence of the YMES sequence adjacent to RAD significantly increases the .

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