Peptide-Based Multimeric Targeted Contrast Agents

Abstract

Peptides and peptide-targeted multimeric contrast agents are described, as well as methods of making and using the contrast agents.

1 . A purified peptide comprising the amino acid sequence: C-D-Y-Y-G-T-C-X 10  (SEQ ID. NO:17), wherein: 
 X 10  is selected from the group consisting of n(decyl)G, n(4-PhBu)G, MeL, Bpa, Bip, Me-Bip, F(4*), F(3-Me), F(3,4-difluoro), Amh, Hfe, Y(3,5-di-iodo), Pff, 1Nal, d1Nal, and MeL, wherein F(4*) is a phenylalanine substituted at the 4 position with a moiety selected from the group consisting of Et, CF 3 , I, and iPr.    
     
     
         2 . A purified peptide of  claim 1 , comprising the amino acid sequence: C-D-Y-Y-G-T-C-X 10 -X 11  (SEQ ID. NO:18), wherein: 
 X 11  is selected from the group consisting of D, dD, βD, Inp, Nip, Me-D, dC, Cop, and Cmp.    
     
     
         3 . A purified peptide of  claim 2 , comprising the amino acid sequence X 1 -P*-C-D-Y-Y-G-T-C-X 10 -X 11  (SEQ ID. NO:26), wherein: 
 X 1  is any natural or non-natural amino acid; and    P* is proline or a non-natural derivative thereof.    
     
     
         4 . A purified peptide of  claim 1 , having an amino acid sequence selected from the group consisting of:  
       
         
           
                 
                 
                 
                 
               
                     
                     
                 
                     
                   L-P-C-D-Y-Y-G-T-C-n(Decyl)G-dD 
                   (SEQ ID NO:19) 
                     
                 
                     
                     
                 
                     
                   L-P-C-D-Y-Y-G-T-C-n(Decyl)G-D 
                   (SEQ ID NO:20) 
                 
                     
                     
                 
                     
                   L-P-C-D-Y-Y-G-T-C-Bip-D 
                   (SEQ ID NO:21) 
                 
                     
                     
                 
                     
                   L-P-C-D-Y-Y-G-T-C-Bip-dD 
                   (SEQ ID NO:22) 
                 
                     
                     
                 
                     
                   L-P-C-D-Y-Y-G-T-C-MeL-Inp 
                   (SEQ ID NO:23) 
                 
                     
                     
                 
                     
                   L-P-C-D-Y-Y-G-T-C-MeL-Cmp, 
                   (SEQ ID NO:24) 
                 
                     
                   and 
                 
                     
                     
                 
                     
                   L-P-C-D-Y-Y-G-T-C-MeBip-D. 
                   (SEQ ID NO:25) 
                 
                     
                     
                 
             
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
               
            
           
         
       
     
     
         5 . The purified peptide according to any one of claims  1 ,  2 , or  3 , the peptide further capable of forming a disulfide bond under non-reducing conditions.  
     
     
         6 . The purified peptide of  claim 4 , the peptide comprising a disulfide bond.  
     
     
         7 . The purified peptide of  claim 6 , the peptide having a specific binding affinity for fibrin.  
     
     
         8 . A compound comprising the peptide of  claim 1 , linked to a thrombolytic agent.  
     
     
         9 . The compound of  claim 8 , wherein the thrombolytic agent is selected from recombinant tissue type plasminogen activator (tPA), prourokinase, urokinase, streptokinase, anistreplase, staphylokinase, and vampire bat pasminogen activator.