Design and synthesis of peptide inhibitors of blood coagulations.
Inhibition of blood coagulation by peptide aldehydes has been studied. Amino acid sequences were assembled from the P1-P2 portion of the cleavage sites(s) of clotting factors and residues selected experimentally. The thrombin-fibrinogen reaction could effectively be inhibited by D-Phe-Pro-Arg-H (GYKI-14,166) and Boc-D-Phe-Pro-Arg-H (GYKI-14,451). Plasmin digestion of fibrin could be retarded by Boc-Gln-Phe-Lys-H (GYKI-14,605) derived from a susceptible fragment, i.e. Asn-Phe-Lys decreases to Ser. However, such peptides could not retard the zymogen activations proceeding in Ca++ complexes (which seemed to be uneffected by heparin-antithrombin III, too). Inhibition of enzymes by peptide aldehydes showed marked substrate dependence.
D000595:Amino Acid Sequence; D000925:Anticoagulants / Q000494:pharmacology; D001777:Blood Coagulation; D055598:Chemical Phenomena; D002621:Chemistry; D005341:Fibrinolysin / Q000037:antagonists & inhibitors; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000494:pharmacology; D011480:Protease Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D013917:Thrombin / Q000037:antagonists & inhibitors; D014568:Urokinase-Type Plasminogen Activator / Q000037:antagonists & inhibitors
D000925:Anticoagulants; D009842:Oligopeptides; D011480:Protease Inhibitors; C035202:H-D-Phe-Pro-arginal; C030798:tert-butyloxycarbonyl-phenylalanyl-prolyl-arginal; D013917:Thrombin; D005341:Fibrinolysin; D014568:Urokinase-Type Plasminogen Activator