F11 receptor (F11R) antagonists as therapeutic agents

Abstract

The present invention provides a cell adhesion molecule (CAM), designated F11 receptor (F11R), which is a member of the immunoglobulin super family localized on the surface of human platelets, and determined to effect platelet aggregation, secretion, platelet spreading and cellular adhesion. F11R-antagonists and methods for the prevention and treatment of thrombosis, atherosclerosis, heart attacks, stroke and other clinical disorders involving thrombus formation are also provided.

1 . An isolated platelet membrane glycoprotein encoded by a sequence set forth in SEQ ID NO: 7.  
     
     
         2 . A composition comprising the glycoprotein of  claim 1  and a suitable carrier.  
     
     
         3 . An isolated F11R-antagonist compound or a peptidomimetic thereof.  
     
     
         4 . An isolated F11R-antagonist compound comprising a sequence consisting of the amino acid sequence as set forth in SEQ ID NO: 1 or a peptidomimetic thereof.  
     
     
         5 . An isolated F11R-antagonist compound comprising a sequence consisting of the amino acid sequence as set forth in SEQ ID NO: 4 or a peptidomimetic thereof.  
     
     
         6 . A pharmaceutical composition comprising the isolated F11R-antagonist according to any one of claims  3 - 5 .  
     
     
         7 . A method for treating or preventing thrombus formation, in a patient in need thereof comprising administering a effective amount of the pharmaceutical composition of  claim 6 .  
     
     
         8 . An isolated F11R antagonist comprising SVTVHSSEPEVRIPENNPVKLSC (SEQ ID NO: 1).  
     
     
         9 . An isolated F11R antagonist comprising KSVTREDTGTYTC (SEQ ID NO: 4).  
     
     
         10 . An antibody directed against the antagonist compound of any one of claims  4 - 5 ,  8  or  9 .  
     
     
         11 . A method of treating an F11R mediated disorder in a subject, comprising administering to the subject a therapeutically effective amount of the compound of any of claims  4 - 5 ,  8  or  9  and a pharmaceutically acceptable carrier.  
     
     
         12 . The method of  claim 11 , wherein said F11R mediated disorder is thrombosis, atherosclerosis, heart attack, excessive bleeding and stroke.  
     
     
         13 . A method of treating a F11R mediated disorder comprising blocking the adhesion of platelets to endothelial cells by the administration of an F11R antagonist.