Effect of synthetic peptides corresponding to residues 313-332 of the αIIb subunit on platelet activation and fibrinogen binding to αIIbβ3

John V. Mitsios, Afroditi P. Tambaki, Morfis Abatzis, Nikolaos Biris, Maria Sakarellos-Daitsiolis, Constantinos Sakarellos, Ketty Soteriadou, John Goudevenos, Moses Elisaf, Demokritos Tsoukatos, Vassilios Tsikaris, Alexandros D. Tselepis

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26 Scopus citations


The platelet integrin receptor αIIbβ3 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 (313-332) sequence of the αIIb subunit plays an important role in platelet activation, fibrinogen binding and αIIbβ3-mediated outside-in signalling. Furthermore, we recently showed that the 20-residue peptide (20-mer) αIIb 313-332, is a potent inhibitor of platelet aggregation and fibrinogen binding to αIIbβ 3, 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 αIIbβ3, 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 peptide's biological potency. The development of such inhibitors derived from the 313-332 region of the αIIb subunit may be advantageous against the RGD-like antagonists as they could inhibit platelet activation without interacting with αIIbβ3, thus failing to further induce αIIbβ3-mediated outside-in signalling.

Original languageEnglish (US)
Pages (from-to)855-862
Number of pages8
JournalEuropean Journal of Biochemistry
Issue number4
StatePublished - Feb 2004
Externally publishedYes


  • Inhibitors
  • Integrin inhibitors
  • Peptides
  • Platelet activation
  • α β receptor

ASJC Scopus subject areas

  • Biochemistry


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