Antithrombotic agents and methods of use

Abstract

The present invention provides antithrombotic agents useful for the management of cardiovascular disease. The agents of the subject invention are novel cyclic peptides encompassed by the following formula: Y-X.sub.1 -X.sub.2 -G-D-X.sub.3 -X.sub.4 -X.sub.5 -Z (SEQ ID NO. 1). In the above formula, X.sub.2 and X.sub.3 are independently a hydrophobic amino acid and X.sub.4 is a positively charged amino acid. The X.sub.1 and X.sub.5 substituents are independently zero to five amino acids. The amino and carboxy terminal amino acids of a given peptide can be modified according to the substituents Y and Z, respectively. The peptides are cyclized through a bridge between the two amino acids with the peptide, excluding G, D and X.sub.3 in the formation of the bridge. Peptides encompassed by the above formula can be administered in a suitable physiologically acceptable carrier to therapeutically treat thrombosis and conditions resulting from the development of thrombi. Unexpectedly, the above-described agents have a higher apparent affinity for GP-IIb/IIIa at low calcium concentration, which is typical at the site of a clot, as compared to at higher calcium concentration found elsewhere throughout the whole blood stream.

Dependencies are inferred from the claim text.