Peptidase resistant thrombin receptor peptide ligand

Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Peptide containing doai

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514 18, 530328, 530329, 530330, C07K 706, A61K 3808

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active

054552281

ABSTRACT:
A peptide ligand analogue of peptide ligands derived from thrombin-cleaved thrombin receptor site on platelets resists inactivation by aminopeptidase M by substituting the .beta.-amino acid isoserine for the N-terminal serine of the peptide ligand.

REFERENCES:
Vu, T-K, et al. "Molecular Cloning of a Functional Thrombin Receptor Reveals a Novel Proteolytic Mechanism of Receptor Activation, " Cell, 64, pp. 1057-1068 (1991).
Vasallo, R., et al. "Structure--function Relationships in the Activation of Platelet Thrombin Receptors by Receptor-derived Peptides, " J. Biol. Chem., 267, pp. 6081-6085 (1992).
Hui, K., et al. "Minimal Sequence Requirement of Thrombin Receptor Agonist Peptide, " Biochem. Biophys, Res. Commun., 184, pp. 790-796 (1992).
Sabo, T., et al. "Structure-Activity Studies of the Thrombin Receptor Activating Peptide," Biochem. Biophys. Res. Commun., 188, pp. 604-610 (1992).
Scarborough, R., et al. "Tethered Ligand Agonist Peptides, " J. Biol. Chem., 267, pp. 13146-13149 (1992).
Coller, B., et al. "Thrombin Receptor Activating Peptides: Importance of the N-Terminal Serine and Its Ionization State As Judged by pH Dependence, Nuclear Magnetic Resonance Spectroscopy, and Cleavage by Aminopeptidase M, " Biochem., 31, 11713-20 (1992).
Nose, T., et al. "Enhancement of Thrombin Receptor Activation by Thrombin Receptor-Derived Heptapeptide with Para-Fluorophenylalanime in Place of Phenylalanine, " Biochem. Biophys. Res. Commun., 193, 694-699 (1993).
Chao, B., et al. "Essential Groups in Synthetic Peptides for Activation of the Platelet Thrombin Receptor, " Biochem., 31, 6175-6178 (1992).
Ahmad, S. and Ward, P. "Role of Aminopeptidase Activity in the Regulation of the Pressor Activity of Circulating Angiotensins, " J. Pharmacol. Exp. Ther., 252, 643-650 (1990).
Look, A., et al. "Human Myeloid Plasma Membrane Glyocprotein CD13 (gp150) is Identical to Aminopeptidase M., " J. Clin. Invest., 83, 1299-1307 (1989).
Ward, P., et al. "Metabolism of Vasoactive Peptides by Plasma and Purified Renal Aminopeptidase M., " Biochem Pharmacol., 40, 1725-1732 (1990).
Palmieri, F., et al. "Metabolism of Vasoactive Peptides by Vascular Endothelium and Smooth Muscle Aminopeptidase M., " Biochem. Pharmacol. 38, 173-180 (1989).
Vu, T-K., et al. "Domains Specifying Thrombin-Receptor Interaction, " Nature, 353, 674-677 (1991).
Beer, J., et al. "Immobilized Arg-Gly-Asp (RGD) Peptides of Varying Lengths as Structural Probes of the Platelet Glycoprotein IIb/IIIa Receptor, " Blood 79, 117-128 (1992).

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