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

Stanica, R. M./ Benaki, D./ Rodis, F. I./ Mikros, E./ Tsoukatos, D./ Tselepis, A./ Tsikaris, V.

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.
Institution and School/Department of submitter: Πανεπιστήμιο Ιωαννίνων. Σχολή Θετικών Επιστημών. Τμήμα Χημείας
Keywords: alpha(iib) binding sites,arginine interactions,aspartic acid interactions,fibrinogen inhibitors,integrin alpha(iib)beta(3),nmr of peptides,rgd conformation,sars,fibrinogen binding,integrin alpha(iib)beta(3),thrombasthenia,activation,arginine,conformations,guanidinium,gpiib/iiia,receptor,h-1-nmr
ISSN: 1075-2617
Link: <Go to ISI>://000260926800005
Publisher: European Peptide Society and John Wiley & Sons, Ltd.
Appears in Collections:Άρθρα σε επιστημονικά περιοδικά ( Ανοικτά)

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