Premium
Peptides and pseudopeptides incorporating D ‐Phe–Pro–Arg and Arg–Gly–Asp lead sequences as potential antithrombotic agents
Author(s) -
Ilaš Janez,
Hudecz Ferenc,
SüliVargha Helga,
Kikelj Danijel
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.1030
Subject(s) - chemistry , antithrombotic , lead (geology) , pharmacology , biochemistry , combinatorial chemistry , medicine , biology , paleontology
Peptide leads D ‐Phe–Pro–Arg for thrombin inhibition and Arg–Gly–Asp for antagonistic activity on fibrinogen receptor were combined in one molecule in order to produce compounds capable of acting both as thrombin inhibitors and as fibrinogen receptor antagonists. Peptide conjugate 7 possessing both leads joined by a tetraglycine linker as well as tripeptides and peptidomimetics with highly overlapped D ‐Phe–Pro–Arg and Arg–Gly–Asp pharmacophore groups were prepared. Conjugate 7 was found to possess antagonistic activity on fibrinogen receptor, but was unexpectedly inactive as thrombin inhibitor. Compound 9 comprising of highly integrated D ‐Phe–Pro–Arg and Arg–Gly–Asp pharmacophore groups was found to possess a moderate but well balanced thrombin inhibitory and fibrinogen receptor antagonistic activity. Copyright © 2008 European Peptide Society and John Wiley & Sons, Ltd.