Metallopeptide gamma-Melanocyte Stimulating Hormone Compounds

Abstract

Metallopeptides with a sequence of a biologically active gamma-melanocyte stimulating hormone sequence of length n residues, wherein a residue including a nitrogen atom and sulfur atom each available for complexation to a metal ion is inserted at any position from between the two and three position to the C-terminus side of the n position, or alternatively is substituted for the residue at any position from the three position to the n position, with a metal ion complexed thereto, with any proline (Pro) residue which is either of the two residues on the immediately adjacent N-terminus side of the inserted or substituent residue comprising a nitrogen atom and sulfur atom available for complexation to a metal ion is substituted with a homolog.

1 . A metallopeptide comprising a biologically active gamma-melanocyte stimulating hormone (γ-MSH) sequence of length n residues, wherein a residue comprising a nitrogen atom and sulfur atom each available for complexation to a metal ion is inserted at any position from between the two and three position to the C-terminus side of the n position, with a metal ion complexed thereto, wherein any proline (Pro) residue which is either of the two residues on the immediately adjacent N-terminus side of the inserted residue comprising a nitrogen atom and sulfur atom available for complexation to a metal ion is substituted with a homolog. 
     
     
         2 . The metallopeptide of  claim 1  wherein the metal ion is rhenium. 
     
     
         3 . The metallopeptide of  claim 1  wherein the γ-MSH sequence is Tyr-Val-Nle-Gly-His-D-Phe-Arg-Trp-Asp-Arg-Phe-NH 2 . 
     
     
         4 . The metallopeptide of  claim 3  wherein the residue comprising a nitrogen and sulfur atom is L-Cys and the metallopeptide sequence is selected from the group consisting of: 
       
         
           
                 
                 
               
                   Tyr-Val-Nle-Gly-His-D-Phe-Arg-Trp-Asp-Arg-Phe-Cys- 
                     
                 
                   NH 2 , 
                 
                     
                 
                   Tyr-Val-Nle-Gly-His-D-Phe-Arg-Trp-Asp-Arg-Cys-Phe- 
                 
                   NH 2 , 
                 
                     
                 
                   Tyr-Val-Nle-Gly-His-D-Phe-Arg-Trp-Asp-Cys-Arg-Phe- 
                 
                   NH 2 , 
                 
                     
                 
                   Tyr-Val-Nle-Gly-His-D-Phe-Arg-Trp-Cys-Asp-Arg-Phe- 
                 
                   NH 2 , 
                 
                     
                 
                   Tyr-Val-Nle-Gly-His-D-Phe-Arg-Cys-Trp-Asp-Arg-Phe- 
                 
                   NH 2 , 
                 
                     
                 
                   Tyr-Val-Nle-Gly-His-D-Phe-Cys-Arg-Trp-Asp-Arg-Phe- 
                 
                   NH 2 , 
                 
                     
                 
                   Tyr-Val-Nle-Gly-His-Cys-D-Phe-Arg-Trp-Asp-Arg-Phe- 
                 
                   NH 2 , 
                 
                     
                 
                   Tyr-Val-Nle-Gly-His-Cys-D-Phe-Arg-Trp-Asp-Arg-Phe- 
                 
                   NH 2 , 
                 
                     
                 
                   Tyr-Val-Nle-Gly-Cys-His-D-Phe-Arg-Trp-Asp-Arg-Phe- 
                 
                   NH 2 , 
                 
                     
                 
                   Tyr-Val-Nle-Cys-Gly-His-D-Phe-Arg-Trp-Asp-Arg-Phe- 
                 
                   NH 2 , 
                 
                   or 
                 
                     
                 
                   Tyr-Val-Cys-Nle-Gly-His-D-Phe-Arg-Trp-Asp-Arg-Phe- 
                 
                   NH 2 . 
                 
             
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
               
            
           
         
       
     
     
         5 . The metallopeptide of  claim 1 , wherein the γ-MSH sequence is Tyr-Val-Nle-Gly-His-Phe-Arg-Trp-Asp-Arg-Phe-NH 2  (SEQ ID NO:14). 
     
     
         6 . The metallopeptide of  claim 5  wherein the residue comprising a nitrogen and sulfur atom is L-Cys and the metallopeptide sequence is selected from the group consisting of: 
       
         
           
                 
                 
               
                   (SEQ ID NO: 15) 
                     
                 
                 
                 
               
                   Tyr-Val-Nle-Gly-His-Phe-Arg-Trp-Asp-Arg-Phe-Cys- 
                     
                 
                   NH 2 , 
                 
                     
                 
                 
                 
               
                   (SEQ ID NO: 16) 
                     
                 
                 
                 
               
                   Tyr-Val-Nle-Gly-His-Phe-Arg-Trp-Asp-Arg-Cys-Phe- 
                     
                 
                   NH 2 , 
                 
                     
                 
                 
                 
               
                   (SEQ ID NO: 17) 
                     
                 
                 
                 
               
                   Tyr-Val-Nle-Gly-His-Phe-Arg-Trp-Asp-Cys-Arg-Phe- 
                     
                 
                   NH 2 , 
                 
                     
                 
                 
                 
               
                   (SEQ ID NO: 18) 
                     
                 
                 
                 
               
                   Tyr-Val-Nle-Gly-His-Phe-Arg-Trp-Cys-Asp-Arg-Phe- 
                     
                 
                   NH 2 , 
                 
                     
                 
                 
                 
               
                   (SEQ ID NO: 19) 
                     
                 
                 
                 
               
                   Tyr-Val-Nle-Gly-His-Phe-Arg-Cys-Trp-Asp-Arg-Phe- 
                     
                 
                   NH 2 , 
                 
                     
                 
                 
                 
               
                   (SEQ ID NO: 20) 
                     
                 
                 
                 
               
                   Tyr-Val-Nle-Gly-His-Phe-Cys-Arg-Trp-Asp-Arg-Phe- 
                     
                 
                   NH 2 , 
                 
                     
                 
                 
                 
               
                   (SEQ ID NO: 21) 
                     
                 
                 
                 
               
                   Tyr-Val-Nle-Gly-His-Cys-Phe-Arg-Trp-Asp-Arg-Phe- 
                     
                 
                   NH 2 , 
                 
                     
                 
                 
                 
               
                   (SEQ ID NO: 22) 
                     
                 
                 
                 
               
                   Tyr-Val-Nle-Gly-Cys-His-Phe-Arg-Trp-Asp-Arg-Phe- 
                     
                 
                   NH 2 , 
                 
                     
                 
                 
                 
               
                   (SEQ ID NO: 23) 
                     
                 
                 
                 
               
                   Tyr-Val-Nle-Cys-Gly-His-Phe-Arg-Trp-Asp-Arg-Phe- 
                     
                 
                   NH 2 , 
                 
                   or 
                 
                     
                 
                 
                 
               
                   (SEQ ID NO: 24) 
                     
                 
                 
                 
               
                   Tyr-Val-Cys-Nle-Gly-His-Phe-Arg-Trp-Asp-Arg-Phe- 
                     
                 
                   NH 2 . 
                 
             
                
               
            
             
                
                
                
               
            
             
                
               
            
             
                
                
                
               
            
             
                
               
            
             
                
                
                
               
            
             
                
               
            
             
                
                
                
               
            
             
                
               
            
             
                
                
                
               
            
             
                
               
            
             
                
                
                
               
            
             
                
               
            
             
                
                
                
               
            
             
                
               
            
             
                
                
                
               
            
             
                
               
            
             
                
                
                
                
               
            
             
                
               
            
             
                
                
               
            
           
         
       
     
     
         7 . A metallopeptide comprising a biologically active γ-MSH sequence of length n residues, wherein a residue comprising a nitrogen atom and sulfur atom each available for complexation to a metal ion is substituted for the residue at any position from the three position to the n position, with a metal ion complexed thereto, wherein any Pro residue which is either of the two residues on the immediately adjacent N-terminus side of the substituent residue comprising a nitrogen atom and sulfur atom available for complexation to a metal ion is substituted with a homolog. 
     
     
         8 . The metallopeptide of  claim 7  wherein the metal ion is rhenium. 
     
     
         9 . The metallopeptide of  claim 8  wherein the γ-MSH sequence is Tyr-Val-Nle-Gly-His-D-Phe-Arg-Trp-Asp-Arg-Phe-NH 2 . 
     
     
         10 . The metallopeptide of  claim 9  wherein the residue comprising a nitrogen and sulfur atom is L-Cys and the metallopeptide sequence is selected from the group consisting of: 
       
         
           
                 
                 
               
                   Tyr-Val-Nle-Gly-His-D-Phe-Arg-Trp-Asp-Arg-Cys-NH 2 , 
                     
                 
                     
                 
                   Tyr-Val-Nle-Gly-His-D-Phe-Arg-Trp-Asp-Cys-Phe-NH 2 , 
                 
                     
                 
                   Tyr-Val-Nle-Gly-His-D-Phe-Arg-Trp-Cys-Arg-Phe-NH 2 , 
                 
                     
                 
                   Tyr-Val-Nle-Gly-His-D-Phe-Arg-Cys-Asp-Arg-Phe-NH 2 , 
                 
                     
                 
                   Tyr-Val-Nle-Gly-His-D-Phe-Cys-Trp-Asp-Arg-Phe-NH 2 , 
                 
                     
                 
                 
                 
               
                   (SEQ ID NO: 66) 
                     
                 
                 
                 
               
                   Tyr-Val-Nle-Gly-His-Cys-Arg-Trp-Asp-Arg-Phe-NH 2 , 
                     
                 
                     
                 
                   Tyr-Val-Nle-Gly-Cys-D-Phe-Arg-Trp-Asp-Arg-Phe-NH 2 , 
                 
                     
                 
                   Tyr-Val-Nle-Cys-His-D-Phe-Arg-Trp-Asp-Arg-Phe-NH 2 , 
                 
                   or 
                 
                     
                 
                   Tyr-Val-Cys-Gly-His-D-Phe-Arg-Trp-Asp-Arg-Phe-NH 2 .