| 摘要 |
<p>This invention relates to novel, biologically active molecules which bind to and inhibit the thrombin receptor. The molecules of this invention are characterized by a portion which binds to the 'hirudin-like' domain of the thrombin receptor (amino acids 52-69). These thrombin receptor antagonists are further characterized by their ability to inhibit thrombin-induced platelet aggregation without affecting the catalytic activity of thrombin. More specifically, the thrombin receptor antagonist of this invention comprises the formula: Y-A1-W-X1-X2-X3-X4-A2-Z; wherein Y is hydrogen, a peptide of from 1 to 10 amino acids, either the same or different, or an acyl or alkyl chain comprising from 1 to 30 backbone atoms; each of A1 and A2, either the same or different, are selected from the group consisting of a positively charged amino acid and an acyl or alkyl chain comprising from 1 to 10 backbone atoms and a positively charged side group; W and each X is any amino acid, either the same or different; and Z is OH, a peptide of from 1 to 11 amino acids, either the same or different, or an acyl or alkyl chain comprising from 1 to 33 backbone atoms, with the proviso that at least one of W, X1 and X2 is not a basic amino acid; and wherein said antagonist is optionally cyclized by a covalent bond between Y and Z. This invention also relates to compositions and methods which employ these molecules for therapeutic and prophylactic purposes.</p> |
