Method and composition for treating thrombosis
AssigneeLa Jolla Cancer Research Foundation
InventorsMichael D. Pierschbacher, Soan Cheng, William S. Craig, Juerg F. Tschopp
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Abstract
The invention provides cyclic peptides which inhibit platelet aggregation without causing prolonged bleeding time. The invention provides RGD or KGD containing peptides which are cyclized and contain hydrophobic amino acids adjacent to the carboxy terminus of the RGD sequence. Peptides of this nature are also provided which contain in addition to the hydrophobic amino acid an adjacent positively charged amino acid. Such peptides have a high affinity for the receptor IIb/IIIa and a low affinity for the fibronectin and vitronectin receptors. Such peptides can be administered in a suitable physiologically acceptable carrier to therapeutically treat thrombosis.
Claims22
A cyclic peptide having the structure:
- X.sub.1 X.sub.2 X.sub.3 X.sub.4 G D X.sub.5 X.sub.6 X.sub.7 X.sub.8
- wherein
- X.sub.1 and X.sub.8 are 0 to 20 amino acids;
- X.sub.2 is 0 or an amino acid capable of forming a bridge;
- X.sub.3 is 0 to 10 amino acids;
- X.sub.4 is a positively charged amino acid;
- X.sub.5 is a hydrophobic amino acid;
- X.sub.6 is a positively charged amino acid;
- and
- X.sub.7 is an amino acid capable of forming a bridge, wherein the hydrophobic amino acid is non-polar and the cyclic peptide inhibits platelet aggregation activity without substantially prolonging bleeding time.
A cyclic RGD-containing peptide having the structure Ac-CRGD(O-Me-Y)P(Pen)-R-NH.sub.2.
An RGD-containing peptide having the structure Ac-RGD(O-n-butyl-Y)-R-NH.sub.2.
Dependencies are inferred from the claim text.