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  • Title: Peptides and pseudopeptides incorporating D-Phe-Pro-Arg and Arg-Gly-Asp lead sequences as potential antithrombotic agents.
    Author: Ilas J, Hudecz F, Süli-Vargha H, Kikelj D.
    Journal: J Pept Sci; 2008 Aug; 14(8):946-53. PubMed ID: 18383437.
    Abstract:
    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.
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