Structure-activity relationships of alpha(IIb) 313-320 derived peptide inhibitors of human platelet aggregation (EN)

Stanica, R. M. (EN)

Πανεπιστήμιο Ιωαννίνων. Σχολή Θετικών Επιστημών. Τμήμα Χημείας (EL)

Stanica, R. M. (EN)

The alpha(IIb)beta(3) receptor, which is the most abundant receptor on the surface of platelets, can interact with a variety of adhesive proteins including fibrinogen, fibronectin and the von Willebrand factor. Fibrinogen binding on alpha(IIb)beta(3) is an event essential for platelet aggregation and thrombus formation. Mapping of the fibrinogen-binding domains on alpha(IIb) subunit suggested the sequence 313-332 as a possible binding site. This region was restricted to sequence alpha(IIb) 313-320 (Y(313)MESRADR(320)) using synthetic octapeptides overlapping by six residues. The YMESRADR octapeptide inhibits ADP-stimulated human platelets aggregation and binds to immobilized fibrinogen. In this study, we used the Ala scanning methodology within the sequence 313-320 aiming to evaluate the contribution of each amino acid in inhibiting platelet aggregation. It was found that the substitution of Y-313, M-314, E-315 or S-316 by A does not affect the activity of the parent, octapeptide. The-RADR-motif seems to be the most essential for the biological activity of the all,, 313-320 site. The conformational analysis of the YAESRADR, YMESAADR and YMESRAAR analogs by using NMR spectroscopy and distance geometry calculations revealed significant differences in their conformational states. in DMSO-d(6). Copyright (C) 2008 European Peptide Society and John Wiley & Sons, Ltd. (EN)

alpha(iib) binding sites (EN)

Πανεπιστήμιο Ιωαννίνων

Ιδρυματικό Αποθετήριο Ολυμπιάς

Σχολή Θετικών Επιστημών

Άρθρα σε επιστημονικά περιοδικά ( Ανοικτά)

ΑΠΟΘΕΤΗΡΙΟ "ΟΛΥΜΠΙΑΣ"

Τμήμα Χημείας

Journal of Peptide Science (EN)

Αγγλική γλώσσα

2008

http://olympias.lib.uoi.gr/jspui/handle/123456789/9313

<Go to ISI>://000260926800005

European Peptide Society and John Wiley & Sons, Ltd. (EN)