@article{3062276,
    title = "Structure-activity relationships of αIIb 313-320 derived peptide inhibitors of human platelet aggregation",
    author = "Stanica, R.M. and Benaki, D. and Rodis, F.I. and Mikros, E. and Tsoukatos, D. and Tselepis, A. and Tsikaris, V.",
    journal = "Journal of Peptide Science",
    year = "2008",
    volume = "14",
    number = "11",
    pages = "1195-1202",
    issn = "1075-2617, 1099-1387",
    doi = "10.1002/psc.1060",
    keywords = "alanine;  alanylmethionylglutamylserylarginylalanylaspartylarginine;  fibrinogen;  fibrinogen receptor;  fibrinogen receptor antagonist;  glutamic acid;  methionine;  octapeptide;  peptide derivative;  serine;  synthetic peptide;  tyrosine;  tyrosylalanylglutamylserylarginylalanylaspartylarginine;  tyrosylmethionylalanylserylarginylalanylaspartylarginine;  tyrosylmethionylglutamylalanylarginylalanylaspartylarginine;  tyrosylmethionylglutamylserylalanylalanylaspartylarginine;  tyrosylmethionylglutamylserylarginylalanylalanylarginine;  tyrosylmethionylglutamylserylarginylalanylaspartylalanine;  tyrosylmethionylglutamylserylarginylalanylaspartylarginine;  tyrosylmethionylglutamylserylarginylalanylaspartylarginyllysylleucylalanylglutamylvalylglycylarginylvalyltyrosylleucylphenylalanylleucine;  unclassified drug, amino acid sequence;  amino acid substitution;  article;  biological activity;  controlled study;  drug protein binding;  human;  nuclear magnetic resonance spectroscopy;  peptide synthesis;  priority journal;  protein conformation;  protein function;  protein structure;  sequence analysis;  signal transduction;  structure activity relation;  thrombocyte aggregation inhibition, Arginine;  Aspartic Acid;  Humans;  Integrin beta3;  Magnetic Resonance Spectroscopy;  Molecular Conformation;  Oligopeptides;  Peptides;  Platelet Aggregation;  Platelet Aggregation Inhibitors;  Platelet Membrane Glycoprotein IIb;  Protein Conformation;  Spectrometry, Mass, Electrospray Ionization;  Structure-Activity Relationship;  von Willebrand Factor",
    abstract = "The αIIbβ3 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 IIbβ3 is an event essential for platelet aggregation and thrombus formation. Mapping of the fibrinogen-binding domains on αIIb subunit suggested the sequence 313-332 as a possible binding site. This region was restricted to sequence αIIb 313-320 (Y313MESRADR320) 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 Y313, M314, E315 or S316 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 αIIb 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-d6. Copyright © 2008 European Peptide Society and John Wiley & Sons, Ltd."
}