Premium
Structure–activity relationships of α IIb 313–320 derived peptide inhibitors of human platelet aggregation
Author(s) -
Stanica Ruxandra Maria,
Benaki Dimitra,
Rodis Foteini I.,
Mikros Emmanuel,
Tsoukatos Dimokritos,
Tselepis Alexandros,
Tsikaris Vasilios
Publication year - 2008
Publication title -
journal of peptide science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.475
H-Index - 66
eISSN - 1099-1387
pISSN - 1075-2617
DOI - 10.1002/psc.1060
Subject(s) - chemistry , platelet , fibrinogen , peptide , stereochemistry , fibronectin , peptide sequence , von willebrand factor , binding site , receptor , nuclear magnetic resonance spectroscopy , amino acid residue , biochemistry , amino acid , platelet aggregation , platelet activation , biophysics , biology , immunology , gene , extracellular matrix
The α IIb β 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 α IIb β 3 is an event essential for platelet aggregation and thrombus formation. Mapping of the fibrinogen‐binding domains on α IIb subunit suggested the sequence 313–332 as a possible binding site. This region was restricted to sequence α 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 α IIb 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 © 2008 European Peptide Society and John Wiley & Sons, Ltd.