Modular Imaging Agents Containing Amino Acids and Peptides

Abstract

Targeted molecular imaging agents (TMIAs) are derived from coupling together pre-formed amino acids with imaging agents attached to their side chains. These peptide-based imaging agents may be synthesized from a single or multiple preformed amino acids containing multi-modal, multi-chelated metal, multi-dye imaging agents, or combinations of these, on the side chains of resultant peptides. These imaging amino acids or peptides may be conjugated directly, or activated, or attached to linkers to which targeting groups, such as peptides, proteins, antibodies, aptamers, or small molecule inhibitors, may be conjugated in the final steps of the synthesis to form a wide variety of TMIAs.

What is claimed is: 
     
         1 . A compound comprising: 
       
         
           
           
               
               
           
         
       
       wherein:
 A is (CH 2 ) n , wherein n is 1-10; 
 B is a moiety selected from H, Fmoc, Cbz, Boc, Mtt, or Alloc; 
 C is a moiety selected from OH, OR 5 , NH 2 , or an activating group; 
 D is a dye, or metal-chelate complex, attached directly, or via a linker; 
 R 1  is H, CH 3 , or CH 2 CH 3 ; 
 R 2  is H, CH 3 , or CH 2 CH 3 ; 
 R 3  is H, CH 3 , or CH 2 CH 3 ; 
 R 4  is H, CH 3 , or CH 2 CH 3 ; and 
 R 5  is H, CH 3 , or CH 2 CH 3 . 
 
     
     
         2 . The compound according to  claim 1 , comprising: 
       
         
           
           
               
               
           
         
       
       wherein:
 A is (CH 2 ) n , wherein n is 1-4; 
 B is a moiety selected from H, Fmoc, Cbz, Boc, Mtt, or Alloc; 
 C is a moiety selected from OH, OR 5 , NH 2 , or an activating group; 
 D is a dye, or metal-chelate complex, attached directly, or via a linker; 
 R 1  is H CH 3 ; 
 R 2  is H or CH 3 ; and 
 R 5  is H, CH 3 , or CH 2 CH 3 . 
 
     
     
         3 . The compound according to  claim 2 , wherein:
 A is (CH 2 ) n , wherein n is 1-4;   B is a moiety selected from H, Fmoc, Boc, or Cbz;   C is a moiety selected from OH, NH 2 , or an activating group;   D is a dye, or metal-chelate complex, attached directly, or via a linker;   R 1  is H; and   R 2  is H.   
     
     
         4 . The compound according to  claim 3 , wherein A is (CH 2 ) n , wherein n is 4; B is Fmoc; C is NH 2 ; D is DOTA-Gd; R 1  is H; and R 2  is H. 
     
     
         5 . The compound according to  claim 3 , wherein A is (CH 2 ) n , wherein n is 4; B is H; C is NH 2 , D is DOTA-Gd; R 1  is H; and R 2  is H. 
     
     
         6 . The compound according to  claim 3 , wherein A is (CH 2 ) n , wherein n is 4; B is Fmoc; C is OH; D is DOTA-Gd; R 1  is H; and R 2  is H. 
     
     
         7 . The compound according to  claim 3 , wherein A is (CH 2 ) n , wherein n is 4; B is Fmoc; C is NH 2 ; D is DOTA-Eu 3+ ; R 1  is H; and R 2  is H. 
     
     
         8 . The compound according to  claim 3 , wherein A is (CH 2 ) n , wherein n is 4; B is Fmoc; C is NH 2 ; D is DOTA-Eu 2+ ; R 1  is H; and R 2  is H. 
     
     
         9 . The compound according to  claim 3 , wherein A is (CH 2 ) n , wherein n is 4; B is Fmoc; C is NH 2 ; D is DOTA-Ce; R 1  is H; and R 2  is H. 
     
     
         10 . The compound according to  claim 3 , wherein A is (CH 2 ) n , wherein n is 4; B is Fmoc; C is NH 2 ; D is DOTA-Cu; R 1  is H; and R 2  is H. 
     
     
         11 . The compound according to  claim 3 , wherein A is (CH 2 ) n , wherein n is 4; B is Fmoc; C is OH; D is Cy5.5; R 1  is H; and R 2  is H. 
     
     
         12 . The compound according to  claim 3 , wherein A is (CH 2 ) n , wherein n is 4; B is Fmoc; C is NH 2 ; D is Cy5.5; R 1  is H; and R 2  is H. 
     
     
         13 . The compound according to  claim 3 , wherein A is (CH 2 ) n , wherein n is 4; B is H; C is NH 2 ; D is Cy5.5; R 1  is H; and R 2  is H. 
     
     
         14 . The compound according to  claim 3 , wherein A is (CH 2 ) n , wherein n is 4; B is Fmoc; C is OH; D is Cy7; R 1  is H; and R 2  is H. 
     
     
         15 . The compound according to  claim 3 , wherein A is (CH 2 ) n , wherein n is 4; B is Fmoc; C is NH 2 ; D is Cy7; R 1  is H; and R 2  is H. 
     
     
         16 . The compound according to  claim 3 , wherein A is (CH 2 ) n , wherein n is 4; B is H; C is NH 2 ; D is Cy7; R 1  is H; and R 2  is H. 
     
     
         17 . A compound according to  claim 3 , wherein A is (CH 2 ) n , wherein n is 4; B is H; C is OH; D is Cy7; R 1  is H; and R 2  is H. 
     
     
         18 . The compound according to  claim 3 , wherein A is (CH 2 ) n , wherein n is 1; B is Cbz; C is OBz; D is DO3A-Gd; R 1  is H; and R 2  is H. 
     
     
         19 . The compound according to  claim 3 , wherein A is (CH 2 ) n , wherein n is 1; B is H; C is OH; D is DO3A-Gd; R 1  is H; and R 2  is H. 
     
     
         20 . A compound comprising: 
       
         
           
           
               
               
           
         
       
       wherein:
 A and A′ are each independently (CH 2 ) n , wherein n is 1-10; 
 B is a moiety selected from H, Fmoc, Cbz, Boc, Mtt, or Alloc; 
 C is a moiety selected from OH, OR 5 , NH 2 , or an activating group; 
 D and D′ are each independently a dye, or metal-chelate complex, attached directly, or via a linker; 
 R 1  and R 1 ′ are each independently H, CH 3 , or CH 2 CH 3 ; 
 R 2  and R 2 ′ are each independently H, CH 3 , or CH 2 CH 3 , 
 R 3  is H, CH 3 , or CH 2 CH 3 ; and 
 R 5  is H, CH 3 , or CH 2 CH 3 .