Effect of synthetic peptides corresponding to residues 313-332 of the alpha(IIb) subunit on platelet activation and fibrinogen binding to alpha(IIb)beta(3)
Φόρτωση...
Ημερομηνία
Τίτλος Εφημερίδας
Περιοδικό ISSN
Τίτλος τόμου
Εκδότης
Blackwell Publishing
Περίληψη
Τύπος
Είδος δημοσίευσης σε συνέδριο
Είδος περιοδικού
peer reviewed
Είδος εκπαιδευτικού υλικού
Όνομα συνεδρίου
Όνομα περιοδικού
European Journal of Biochemistry
Όνομα βιβλίου
Σειρά βιβλίου
Έκδοση βιβλίου
Συμπληρωματικός/δευτερεύων τίτλος
Περιγραφή
The platelet integrin receptor alpha(IIb)beta(3) 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 alpha(IIb) subunit plays an important role in platelet activation, fibrinogen binding and alpha(IIb)beta(3)-mediated outside-in signalling. Furthermore, we recently showed that the 20-residue peptide (20-mer) alpha(IIb) 313-332, is a potent inhibitor of platelet aggregation and fibrinogen binding to alpha(IIb)beta(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 alpha(IIb)beta(3), 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 alpha(IIb) subunit may be advantageous against the RGD-like antagonists as they could inhibit platelet activation without interacting with alpha(IIb)beta(3), thus failing to further induce alpha(IIb)beta(3)-mediated outside-in signalling.
Περιγραφή
Λέξεις-κλειδιά
integrin inhibitors, peptides, platelet activation inhibitors, alpha(iib)beta(3) receptor, glycoprotein-iib-iiia, ligand-binding, integrin alpha(iib)beta(3), gamma-chain, receptor, site, recognition, sequence, domain, aggregation
Θεματική κατηγορία
Παραπομπή
Σύνδεσμος
<Go to ISI>://000188819700021
http://onlinelibrary.wiley.com/store/10.1111/j.1432-1033.2004.03990.x/asset/j.1432-1033.2004.03990.x.pdf?v=1&t=h0e0nme0&s=fd1b113d3d77b19eaae24654eacb532c1fcd03f2
http://onlinelibrary.wiley.com/store/10.1111/j.1432-1033.2004.03990.x/asset/j.1432-1033.2004.03990.x.pdf?v=1&t=h0e0nme0&s=fd1b113d3d77b19eaae24654eacb532c1fcd03f2
Γλώσσα
en
Εκδίδον τμήμα/τομέας
Όνομα επιβλέποντος
Εξεταστική επιτροπή
Γενική Περιγραφή / Σχόλια
Ίδρυμα και Σχολή/Τμήμα του υποβάλλοντος
Πανεπιστήμιο Ιωαννίνων. Σχολή Θετικών Επιστημών. Τμήμα Χημείας