US2018362579A1PendingUtilityA1

Aromatic-cationic peptides and uses of same

Assignee: STEALTH PEPTIDES INT INCPriority: Dec 9, 2011Filed: Jan 9, 2018Published: Dec 20, 2018
Est. expiryDec 9, 2031(~5.4 yrs left)· nominal 20-yr term from priority
A61P 43/00A61P 39/06A61P 25/28A61P 3/00C07K 5/1016C07K 5/1019A61K 38/00C07K 5/06086G01N 33/68C07K 5/06095A61K 38/06C07K 5/06078C07K 5/0812C07D 209/16A61K 38/07C07C 229/26C07K 5/10C07K 5/0815C07K 5/08C07K 5/0817C07K 5/06G01N 33/6848
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Claims

Abstract

The disclosure provides compositions and methods relating to aromatic-cationic peptides. The methods comprise administering to the subject an effective amount of an aromatic-cationic peptide to subjects in need thereof. For example, the peptides may be administered to subjects in need of a mitochondrial-targeted antioxidant.

Claims

exact text as granted — not AI-modified
1 . An aromatic-cationic peptide selected from the group consisting of: 
       
         
           
                 
               
                     
                 
                   6-Butyric acid CoQ0-Phe-D-Arg-Phe-Lys-NH 2   
                 
                   6-Decanoic acid CoQ0-Phe-D-Arg-Phe-Lys-NH 2   
                 
                   Arg-Arg-Dmt-Phe 
                 
                   Arg-Cha-Lys 
                 
                   Arg-Dmt 
                 
                   Arg-Dmt-Arg 
                 
                   Arg-Dmt-Lys 
                 
                   Arg-Dmt-Lys-Phe 
                 
                   Arg-Dmt-Lys-Phe-Cys 
                 
                   Arg-Dmt-Phe 
                 
                   Arg-Dmt-Phe-Lys 
                 
                   Arg-Lys-Dmt-Phe 
                 
                   Arg-Lys-Phe-Dmt 
                 
                   Arg-Phe-Dmt-Lys 
                 
                   Arg-Phe-Lys 
                 
                   Arg-Trp-Lys 
                 
                   Arg-Tyr-Lys 
                 
                   Arg-Tyr-Lys-Phe 
                 
                   D-Arg-D-Dmt-D-Lys-D-Phe-NH 2   
                 
                   D-Arg-D-Dmt-D-Lys-L-Phe-NH 2   
                 
                   D-Arg-D-Dmt-L-Lys-D-Phe-NH 2   
                 
                   D-Arg-D-Dmt-L-Lys-L-Phe-NH 2   
                 
                   D-Arg-Dmt-D-Lys-NH 2   
                 
                   D-Arg-Dmt-D-Lys-Phe-NH 2   
                 
                   D-Arg-Dmt-Lys-D-Phe-NH 2   
                 
                   D-Arg-Dmt-Lys-NH 2   
                 
                   D-Arg-Dmt-Lys-Phe-Cys 
                 
                   D-Arg-Dmt-NH 2   
                 
                   D-Arg-L-Dmt-D-Lys-D-Phe-NH 2   
                 
                   D-Arg-L-Dmt-D-Lys-L-Phe-NH 2   
                 
                   D-Arg-L-Dmt-L-Lys-D-Phe-NH 2   
                 
                   D-Arg-Phe-Lys-NH 2   
                 
                   D-Arg-Trp-Lys-NH 2   
                 
                   D-Arg-Tyr-Lys-NH 2   
                 
                   Dmt-Arg 
                 
                   Dmt-Lys 
                 
                   Dmt-Lys-D-Phe-NH 2   
                 
                   Dmt-Lys-NH 2   
                 
                   Dmt-Lys-Phe 
                 
                   Dmt-Lys-Phe 
                 
                   Dmt-Lys-Phe-NH 2   
                 
                   Dmt-Phe-Arg-Lys 
                 
                   H-Arg-D-Dmt-Arg-NH 2   
                 
                   H-Arg-D-Dmt-Lys-NH 2   
                 
                   H-Arg-D-Dmt-Lys-Phe-NH 2   
                 
                   H-Arg-D-Dmt-NH 2   
                 
                   H-Arg-Dmt-Lys-Phe-NH 2   
                 
                   H-D-Arg-2,6-dichloro-L-tyrosine-L-Lys-L-Phe-NH 2   
                 
                   H-D-Arg-2,6-dichlorotyrosine-Lys-Phe-NH 2   
                 
                   H-D-Arg-2,6-difluoro-L-tyrosine-L-Lys-L-Phe-NH 2   
                 
                   H-D-Arg-2,6-difluorotyrosine-Lys-Phe-NH 2   
                 
                   H-D-Arg-2,6-dimethyl-L-phenylalanine-L-Lys-L-Phe-NH 2   
                 
                   H-D-Arg-2,6-dimethylphenylalanine-Lys-Phe-NH 2   
                 
                   H-D-Arg-4-methoxy-2,6-dimethyl-L-tyrosine-L-Lys-L-Phe-NH 2   
                 
                   H-D-Arg-4-methoxy-2,6-dimethyltyrosine-Lys-Phe-NH 2   
                 
                   H-D-Arg-Arg-Dmt-Phe-NH 2   
                 
                   H-D-Arg-Cha-Lys-NH 2   
                 
                   H-D-Arg-D-Dmt-D-Lys-D-Phe-NH 2   
                 
                   H-D-Arg-D-Dmt-Lys-Phe-NH 2   
                 
                   H-D-Arg-D-Dmt-NH 2   
                 
                   H-D-Arg-Dmt-D-Lys-D-Phe-NH 2   
                 
                   H-D-Arg-Dmt-Lys-2,6-dimethylphenylalanine-NH 2   
                 
                   H-D-Arg-Dmt-Lys-3-hydroxyphenylalanine-NH 2   
                 
                   H-D-Arg-Dmt-Lys-NH 2   
                 
                   H-D-Arg-Dmt-Lys-OH 
                 
                   H-D-Arg-Dmt-Lys-Phe-OH 
                 
                   H-D-Arg-Dmt-N6-acetyllysine-Phe-NH 2   
                 
                   H-D-Arg-Dmt-OH 
                 
                   H-D-Arg-Dmt-Phe-Lys-NH 2   
                 
                   H-D-Arg-Dmt-Phe-NH 2   
                 
                   H-D-Arg-D-Phe-L-Lys-L-Phe-NH 2   
                 
                   H-D-Arg-D-Trp-L-Lys-L-Phe-NH 2   
                 
                   H-D-Arg-D-Tyr-L-Lys-L-Phe-NH 2   
                 
                   H-D-Arg-L-Dmt-L-Lys-2,6-dimethyl-L-phenylalanine-NH 2   
                 
                   H-D-Arg-L-Dmt-L-Lys-3-hydroxy-L-phenylalanine-NH 2   
                 
                   H-D-Arg-L-Dmt-L-Lys-D-Dmt-NH 2   
                 
                   H-D-Arg-L-Dmt-L-Lys-D-Trp-NH 2   
                 
                   H-D-Arg-L-Dmt-L-Lys-D-Tyr-NH 2   
                 
                   H-D-Arg-L-Dmt-L-Lys-L-Dmt-NH 2   
                 
                   H-D-Arg-L-Dmt-L-Lys-L-Dmt-NH 2   
                 
                   H-D-Arg-L-Dmt-L-Lys-L-Trp-NH 2   
                 
                   H-D-Arg-L-Dmt-L-Lys-L-Tyr-NH 2   
                 
                   H-D-Arg-L-Dmt-L-Phe-L-Lys-NH 2   
                 
                   H-D-Arg-L-Dmt-N6-acetyl-L-lysine-L-Phe-NH 2   
                 
                   H-D-Arg-L-Lys-L-Dmt-L-Phe-NH 2   
                 
                   H-D-Arg-L-Lys-L-Phe-L-Dmt-NH 2   
                 
                   H-D-Arg-L-Phe-L-Dmt-L-Lys-NH 2   
                 
                   H-D-Arg-L-Phe-L-Lys-L-Dmt-NH 2   
                 
                   H-D-Arg-L-Phe-L-Lys-L-Phe-NH 2   
                 
                   H-D-Arg-L-Trp-L-Lys-L-Phe-NH 2   
                 
                   H-D-Arg-L-Tyr-L-Lys-L-Phe-NH 2   
                 
                   H-D-Arg-Lys-Dmt-Phe-NH 2   
                 
                   H-D-Arg-Lys-Phe-Dmt-NH 2   
                 
                   H-D-Arg-Phe-Dmt-Lys-NH 2   
                 
                   H-D-Arg-Phe-Lys-Dmt-NH 2   
                 
                   H-D-Arg-Tyr-Lys-Phe-NH 2   
                 
                   H-D-Dmt-Arg-NH 2   
                 
                   H-D-His-L-Dmt-L-Lys-L-Phe-NH 2   
                 
                   H-D-Lys-L-Dmt-L-Lys-L-Phe-NH 2   
                 
                   H-Dmt-D-Arg-Lys-Phe-NH 2   
                 
                   H-Dmt-D-Arg-NH 2   
                 
                   H-Dmt-D-Arg-Phe-Lys-NH 2   
                 
                   H-Dmt-D-Phe-Arg-Lys-NH 2   
                 
                   H-Dmt-Lys-D-Arg-Phe-NH 2   
                 
                   H-Dmt-Lys-Phe-D-Arg-NH 2   
                 
                   H-Dmt-Phe-D-Arg-Lys-NH 2   
                 
                   H-Dmt-Phe-Lys-D-Arg-NH 2   
                 
                   H-D-N2-acetylarginine-Dmt-Lys-Phe-NH 2   
                 
                   H-D-N8-acetylarginine-Dmt-Lys-Phe-NH 2   
                 
                   H-D-Phe-D-Arg-D-Phe-D-Lys-NH 2   
                 
                   H-L-Dmt-D-Arg-L-Lys-L-Phe-NH 2   
                 
                   H-L-Dmt-D-Arg-L-Phe-L-Lys-NH 2   
                 
                   H-L-Dmt-L-Lys-D-Arg-L-Phe-NH 2   
                 
                   H-L-Dmt-L-Lys-L-Phe-D-Arg-NH 2   
                 
                   H-L-Dmt-L-Phe-D-Arg-L-Lys-NH 2   
                 
                   H-L-Dmt-L-Phe-L-Lys-D-Arg-NH 2   
                 
                   H-L-His-L-Dmt-L-Lys-L-Phe-NH 2   
                 
                   H-L-Lys-D-Arg-L-Dmt-L-Phe-NH 2   
                 
                   H-L-Lys-D-Arg-L-Phe-L-Dmt-NH 2   
                 
                   H-L-Lys-L-Dmt-D-Arg-L-Phe-NH 2   
                 
                   H-L-Lys-L-Dmt-L-Lys-L-Phe-NH 2   
                 
                   H-L-Lys-L-Dmt-L-Phe-D-Arg-NH 2   
                 
                   H-L-Lys-L-Phe-D-Arg-L-Dmt-NH 2   
                 
                   H-L-Lys-L-Phe-L-Dmt-D-Arg-NH 2   
                 
                   H-L-Phe-D-Arg-L-Dmt-L-Lys-NH 2   
                 
                   H-L-Phe-D-Arg-L-Lys-L-Dmt-NH 2   
                 
                   H-L-Phe-L-Dmt-D-Arg-L-Lys-NH 2   
                 
                   H-L-Phe-L-Dmt-L-Lys-D-Arg-NH 2   
                 
                   H-L-Phe-L-Lys-D-Arg-L-Dmt-NH 2   
                 
                   H-L-Phe-L-Lys-L-Dmt-D-Arg-NH 2   
                 
                   H-Lys-D-Arg-Dmt-Phe-NH 2   
                 
                   H-Lys-D-Arg-Phe-Dmt-NH 2   
                 
                   H-Lys-Dmt-D-Arg-Phe-NH 2   
                 
                   H-Lys-Dmt-Phe-D-Arg-NH 2   
                 
                   H-Lys-D-Phe-Arg-Dmt-NH 2   
                 
                   H-Lys-Phe-D-Arg-Dmt-NH 2   
                 
                   H-Lys-Phe-Dmt-D-Arg-NH 2   
                 
                   H-N2-acetyl-D-arginine-L-Dmt-L-Lys-L-Phe-NH 2   
                 
                   H-N7-acetyl-D-arginine-Dmt-Lys-Phe-NH 2   
                 
                   H-Phe(d5)-D-Arg-Phe(d5)-Lys-NH 2   
                 
                   H-Phe-Arg-Phe-Lys-NH 2   
                 
                   H-Phe-D-Arg-Dmt-Lys-NH 2   
                 
                   H-Phe-D-Arg-Dmt-Lys-NH 2   
                 
                   H-Phe-D-Arg-D-Phe-Lys-NH 2   
                 
                   H-Phe-D-Arg-Lys-Dmt-NH 2   
                 
                   H-Phe-D-Arg-Phe-D-Lys-NH 2   
                 
                   H-Phe-D-Arg-Phe-Lys-Glu-Cys-Gly-NH 2   
                 
                   H-Phe-D-Dmt-Arg-Lys-NH 2   
                 
                   H-Phe-Dmt-D-Arg-Lys-NH 2   
                 
                   H-Phe-Dmt-Lys-D-Arg-NH 2   
                 
                   H-Phe-Lys-D-Arg-Dmt-NH 2   
                 
                   H-Phe-Lys-Dmt-D-Arg-NH 2   
                 
                   L-Arg-D-Dmt-D-Lys-D-Phe-NH 2   
                 
                   L-Arg-D-Dmt-D-Lys-D-Phe-NH 2   
                 
                   L-Arg-D-Dmt-D-Lys-L-Phe-NH 2   
                 
                   L-Arg-D-Dmt-D-Lys-L-Phe-NH 2   
                 
                   L-Arg-D-Dmt-L-Lys-D-Phe-NH 2   
                 
                   L-Arg-D-Dmt-L-Lys-D-Phe-NH 2   
                 
                   L-Arg-D-Dmt-L-Lys-L-Phe-NH 2   
                 
                   L-Arg-D-Dmt-L-Lys-L-Phe-NH 2   
                 
                   L-Arg-L-Dmt-D-Lys-D-Phe-NH 2   
                 
                   L-Arg-L-Dmt-D-Lys-D-Phe-NH 2   
                 
                   L-Arg-L-Dmt-D-Lys-L-Phe-NH 2   
                 
                   L-Arg-L-Dmt-D-Lys-L-Phe-NH 2   
                 
                   L-Arg-L-Dmt-L-Lys-D-Phe-NH 2   
                 
                   L-Arg-L-Dmt-L-Lys-D-Phe-NH 2   
                 
                   L-Arg-L-Dmt-L-Lys-L-Phe-NH 2   
                 
                   L-Arg-L-Dmt-L-Lys-L-Phe-NH 2   
                 
                   Lys-Dmt-Arf 
                 
                   Lys-Dmt-D-Arg-NH 2   
                 
                   Lys-Phe 
                 
                   Lys-Phe-Arg-Dmt 
                 
                   Lys-Phe-NH 2   
                 
                   Lys-Trp-Arg 
                 
                   Lys-Trp-D-Arg-NH 2   
                 
                   Phe-Arg-Dmt-Lys 
                 
                   Phe-Arg-Phe-Lys 
                 
                   Phe-Arg-Phe-Lys 
                 
                   Phe-Arg-Phe-Lys 
                 
                   Phe-Arg-Phe-Lys 
                 
                   Phe-Arg-Phe-Lys 
                 
                   Phe-Arg-Phe-Lys-Glu-Cys-Gly 
                 
                   Phe-Dmt-Arg-Lys 
                 
                   Phe-Lys-Dmt 
                 
                   Phe-Lys-Dmt-NH 2   
                 
                   Succinic monoester CoQ0-Phe-D-Arg-Phe-Lys-NH 2   
                 
                     
                 
             
                
               
               
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
               
            
           
         
       
     
     
         2 . A pharmaceutical composition comprising one or more aromatic-cationic peptides of  claim 1  and pharmaceutically acceptable salts thereof. 
     
     
         3 . The pharmaceutical composition of  claim 2  further comprising a pharmaceutically acceptable carrier. 
     
     
         4 . A method of reducing the number of mitochondria undergoing mitochondrial permeability transition (MPT), or preventing mitochondrial permeability transitioning in a mammal in need thereof, the method comprising administering to the mammal an effective amount of one or more aromatic-cationic peptides of  claim 1 . 
     
     
         5 . A method for reducing oxidative damage in a mammal in need thereof, the method comprising administering to the mammal an effective amount of one or more aromatic-cationic peptides of  claim 1 . 
     
     
         6 . A method for increasing the ATP synthesis rate in a mammal in need thereof, the method comprising administering to the mammal an effective amount of one or more aromatic-cationic peptides of  claim 1 . 
     
     
         7 . A method for determining the presence or amount of an administered aromatic-cationic peptide in a subject, the method comprising: detecting the administered aromatic-cationic peptide in a biological sample from the subject, wherein the aromatic-cationic peptide is selected from the group consisting of: 
       
         
           
                 
               
                     
                 
                   6-Butyric acid CoQ0-Phe-D-Arg-Phe-Lys-NH 2   
                 
                   6-Decanoic acid CoQ0-Phe-D-Arg-Phe-Lys-NH 2   
                 
                   Arg-Arg-Dmt-Phe 
                 
                   Arg-Cha-Lys 
                 
                   Arg-Dmt 
                 
                   Arg-Dmt-Arg 
                 
                   Arg-Dmt-Lys 
                 
                   Arg-Dmt-Lys-Phe 
                 
                   Arg-Dmt-Lys-Phe-Cys 
                 
                   Arg-Dmt-Phe 
                 
                   Arg-Dmt-Phe-Lys 
                 
                   Arg-Lys-Dmt-Phe 
                 
                   Arg-Lys-Phe-Dmt 
                 
                   Arg-Phe-Dmt-Lys 
                 
                   Arg-Phe-Lys 
                 
                   Arg-Trp-Lys 
                 
                   Arg-Tyr-Lys 
                 
                   Arg-Tyr-Lys-Phe 
                 
                   D-Arg-D-Dmt-D-Lys-D-Phe-NH 2   
                 
                   D-Arg-D-Dmt-D-Lys-L-Phe-NH 2   
                 
                   D-Arg-D-Dmt-L-Lys-D-Phe-NH 2   
                 
                   D-Arg-D-Dmt-L-Lys-L-Phe-NH 2   
                 
                   D-Arg-Dmt-D-Lys-NH 2   
                 
                   D-Arg-Dmt-D-Lys-Phe-NH 2   
                 
                   D-Arg-Dmt-Lys-D-Phe-NH 2   
                 
                   D-Arg-Dmt-Lys-NH 2   
                 
                   D-Arg-Dmt-Lys-Phe-Cys 
                 
                   D-Arg-Dmt-NH 2   
                 
                   D-Arg-L-Dmt-D-Lys-D-Phe-NH 2   
                 
                   D-Arg-L-Dmt-D-Lys-L-Phe-NH 2   
                 
                   D-Arg-L-Dmt-L-Lys-D-Phe-NH 2   
                 
                   D-Arg-Phe-Lys-NH 2   
                 
                   D-Arg-Trp-Lys-NH 2   
                 
                   D-Arg-Tyr-Lys-NH 2   
                 
                   Dmt-Arg 
                 
                   Dmt-Lys 
                 
                   Dmt-Lys-D-Phe-NH 2   
                 
                   Dmt-Lys-NH 2   
                 
                   Dmt-Lys-Phe 
                 
                   Dmt-Lys-Phe 
                 
                   Dmt-Lys-Phe-NH 2   
                 
                   Dmt-Phe-Arg-Lys 
                 
                   H-Arg-D-Dmt-Arg-NH 2   
                 
                   H-Arg-D-Dmt-Lys-NH 2   
                 
                   H-Arg-D-Dmt-Lys-Phe-NH 2   
                 
                   H-Arg-D-Dmt-NH 2   
                 
                   H-Arg-Dmt-Lys-Phe-NH 2   
                 
                   H-D-Arg-2,6-dichloro-L-tyrosine-L-Lys-L-Phe-NH 2   
                 
                   H-D-Arg-2,6-dichlorotyrosine-Lys-Phe-NH 2   
                 
                   H-D-Arg-2,6-difluoro-L-tyrosine-L-Lys-L-Phe-NH 2   
                 
                   H-D-Arg-2,6-difluorotyrosine-Lys-Phe-NH 2   
                 
                   H-D-Arg-2,6-dimethyl-L-phenylalanine-L-Lys-L-Phe-NH 2   
                 
                   H-D-Arg-2,6-dimethylphenylalanine-Lys-Phe-NH 2   
                 
                   H-D-Arg-4-methoxy-2,6-dimethyl-L-tyrosine-L-Lys-L-Phe-NH 2   
                 
                   H-D-Arg-4-methoxy-2,6-dimethyltyrosine-Lys-Phe-NH 2   
                 
                   H-D-Arg-Arg-Dmt-Phe-NH 2   
                 
                   H-D-Arg-Cha-Lys-NH 2   
                 
                   H-D-Arg-D-Dmt-D-Lys-D-Phe-NH 2   
                 
                   H-D-Arg-D-Dmt-Lys-Phe-NH 2   
                 
                   H-D-Arg-D-Dmt-NH 2   
                 
                   H-D-Arg-Dmt-D-Lys-D-Phe-NH 2   
                 
                   H-D-Arg-Dmt-Lys-2,6-dimethylphenylalanine-NH 2   
                 
                   H-D-Arg-Dmt-Lys-3-hydroxyphenylalanine-NH 2   
                 
                   H-D-Arg-Dmt-Lys-NH 2   
                 
                   H-D-Arg-Dmt-Lys-OH 
                 
                   H-D-Arg-Dmt-Lys-Phe-OH 
                 
                   H-D-Arg-Dmt-N6-acetyllysine-Phe-NH 2   
                 
                   H-D-Arg-Dmt-OH 
                 
                   H-D-Arg-Dmt-Phe-Lys-NH 2   
                 
                   H-D-Arg-Dmt-Phe-NH 2   
                 
                   H-D-Arg-D-Phe-L-Lys-L-Phe-NH 2   
                 
                   H-D-Arg-D-Trp-L-Lys-L-Phe-NH 2   
                 
                   H-D-Arg-D-Tyr-L-Lys-L-Phe-NH 2   
                 
                   H-D-Arg-L-Dmt-L-Lys-2,6-dimethyl-L-phenylalanine-NH 2   
                 
                   H-D-Arg-L-Dmt-L-Lys-3-hydroxy-L-phenylalanine-NH 2   
                 
                   H-D-Arg-L-Dmt-L-Lys-D-Dmt-NH 2   
                 
                   H-D-Arg-L-Dmt-L-Lys-D-Trp-NH 2   
                 
                   H-D-Arg-L-Dmt-L-Lys-D-Tyr-NH 2   
                 
                   H-D-Arg-L-Dmt-L-Lys-L-Dmt-NH 2   
                 
                   H-D-Arg-L-Dmt-L-Lys-L-Dmt-NH 2   
                 
                   H-D-Arg-L-Dmt-L-Lys-L-Trp-NH 2   
                 
                   H-D-Arg-L-Dmt-L-Lys-L-Tyr-NH 2   
                 
                   H-D-Arg-L-Dmt-L-Phe-L-Lys-NH 2   
                 
                   H-D-Arg-L-Dmt-N6-acetyl-L-lysine-L-Phe-NH 2   
                 
                   H-D-Arg-L-Lys-L-Dmt-L-Phe-NH 2   
                 
                   H-D-Arg-L-Lys-L-Phe-L-Dmt-NH 2   
                 
                   H-D-Arg-L-Phe-L-Dmt-L-Lys-NH 2   
                 
                   H-D-Arg-L-Phe-L-Lys-L-Dmt-NH 2   
                 
                   H-D-Arg-L-Phe-L-Lys-L-Phe-NH 2   
                 
                   H-D-Arg-L-Trp-L-Lys-L-Phe-NH 2   
                 
                   H-D-Arg-L-Tyr-L-Lys-L-Phe-NH 2   
                 
                   H-D-Arg-Lys-Dmt-Phe-NH 2   
                 
                   H-D-Arg-Lys-Phe-Dmt-NH 2   
                 
                   H-D-Arg-Phe-Dmt-Lys-NH 2   
                 
                   H-D-Arg-Phe-Lys-Dmt-NH 2   
                 
                   H-D-Arg-Tyr-Lys-Phe-NH 2   
                 
                   H-D-Dmt-Arg-NH 2   
                 
                   H-D-His-L-Dmt-L-Lys-L-Phe-NH 2   
                 
                   H-D-Lys-L-Dmt-L-Lys-L-Phe-NH 2   
                 
                   H-Dmt-D-Arg-Lys-Phe-NH 2   
                 
                   H-Dmt-D-Arg-NH 2   
                 
                   H-Dmt-D-Arg-Phe-Lys-NH 2   
                 
                   H-Dmt-D-Phe-Arg-Lys-NH 2   
                 
                   H-Dmt-Lys-D-Arg-Phe-NH 2   
                 
                   H-Dmt-Lys-Phe-D-Arg-NH 2   
                 
                   H-Dmt-Phe-D-Arg-Lys-NH 2   
                 
                   H-Dmt-Phe-Lys-D-Arg-NH 2   
                 
                   H-D-N2-acetylarginine-Dmt-Lys-Phe-NH 2   
                 
                   H-D-N8-acetylarginine-Dmt-Lys-Phe-NH 2   
                 
                   H-D-Phe-D-Arg-D-Phe-D-Lys-NH 2   
                 
                   H-L-Dmt-D-Arg-L-Lys-L-Phe-NH 2   
                 
                   H-L-Dmt-D-Arg-L-Phe-L-Lys-NH 2   
                 
                   H-L-Dmt-L-Lys-D-Arg-L-Phe-NH 2   
                 
                   H-L-Dmt-L-Lys-L-Phe-D-Arg-NH 2   
                 
                   H-L-Dmt-L-Phe-D-Arg-L-Lys-NH 2   
                 
                   H-L-Dmt-L-Phe-L-Lys-D-Arg-NH 2   
                 
                   H-L-His-L-Dmt-L-Lys-L-Phe-NH 2   
                 
                   H-L-Lys-D-Arg-L-Dmt-L-Phe-NH 2   
                 
                   H-L-Lys-D-Arg-L-Phe-L-Dmt-NH 2   
                 
                   H-L-Lys-L-Dmt-D-Arg-L-Phe-NH 2   
                 
                   H-L-Lys-L-Dmt-L-Lys-L-Phe-NH 2   
                 
                   H-L-Lys-L-Dmt-L-Phe-D-Arg-NH 2   
                 
                   H-L-Lys-L-Phe-D-Arg-L-Dmt-NH 2   
                 
                   H-L-Lys-L-Phe-L-Dmt-D-Arg-NH 2   
                 
                   H-L-Phe-D-Arg-L-Dmt-L-Lys-NH 2   
                 
                   H-L-Phe-D-Arg-L-Lys-L-Dmt-NH 2   
                 
                   H-L-Phe-L-Dmt-D-Arg-L-Lys-NH 2   
                 
                   H-L-Phe-L-Dmt-L-Lys-D-Arg-NH 2   
                 
                   H-L-Phe-L-Lys-D-Arg-L-Dmt-NH 2   
                 
                   H-L-Phe-L-Lys-L-Dmt-D-Arg-NH 2   
                 
                   H-Lys-D-Arg-Dmt-Phe-NH 2   
                 
                   H-Lys-D-Arg-Phe-Dmt-NH 2   
                 
                   H-Lys-Dmt-D-Arg-Phe-NH 2   
                 
                   H-Lys-Dmt-Phe-D-Arg-NH 2   
                 
                   H-Lys-D-Phe-Arg-Dmt-NH 2   
                 
                   H-Lys-Phe-D-Arg-Dmt-NH 2   
                 
                   H-Lys-Phe-Dmt-D-Arg-NH 2   
                 
                   H-N2-acetyl-D-arginine-L-Dmt-L-Lys-L-Phe-NH 2   
                 
                   H-N7-acetyl-D-arginine-Dmt-Lys-Phe-NH 2   
                 
                   H-Phe(d5)-D-Arg-Phe(d5)-Lys-NH 2   
                 
                   H-Phe-Arg-Phe-Lys-NH 2   
                 
                   H-Phe-D-Arg-Dmt-Lys-NH 2   
                 
                   H-Phe-D-Arg-Dmt-Lys-NH 2   
                 
                   H-Phe-D-Arg-D-Phe-Lys-NH 2   
                 
                   H-Phe-D-Arg-Lys-Dmt-NH 2   
                 
                   H-Phe-D-Arg-Phe-D-Lys-NH 2   
                 
                   H-Phe-D-Arg-Phe-Lys-Glu-Cys-Gly-NH 2   
                 
                   H-Phe-D-Dmt-Arg-Lys-NH 2   
                 
                   H-Phe-Dmt-D-Arg-Lys-NH 2   
                 
                   H-Phe-Dmt-Lys-D-Arg-NH 2   
                 
                   H-Phe-Lys-D-Arg-Dmt-NH 2   
                 
                   H-Phe-Lys-Dmt-D-Arg-NH 2   
                 
                   L-Arg-D-Dmt-D-Lys-D-Phe-NH 2   
                 
                   L-Arg-D-Dmt-D-Lys-D-Phe-NH 2   
                 
                   L-Arg-D-Dmt-D-Lys-L-Phe-NH 2   
                 
                   L-Arg-D-Dmt-D-Lys-L-Phe-NH 2   
                 
                   L-Arg-D-Dmt-L-Lys-D-Phe-NH 2   
                 
                   L-Arg-D-Dmt-L-Lys-D-Phe-NH 2   
                 
                   L-Arg-D-Dmt-L-Lys-L-Phe-NH 2   
                 
                   L-Arg-D-Dmt-L-Lys-L-Phe-NH 2   
                 
                   L-Arg-L-Dmt-D-Lys-D-Phe-NH 2   
                 
                   L-Arg-L-Dmt-D-Lys-D-Phe-NH 2   
                 
                   L-Arg-L-Dmt-D-Lys-L-Phe-NH 2   
                 
                   L-Arg-L-Dmt-D-Lys-L-Phe-NH 2   
                 
                   L-Arg-L-Dmt-L-Lys-D-Phe-NH 2   
                 
                   L-Arg-L-Dmt-L-Lys-D-Phe-NH 2   
                 
                   L-Arg-L-Dmt-L-Lys-L-Phe-NH 2   
                 
                   L-Arg-L-Dmt-L-Lys-L-Phe-NH 2   
                 
                   Lys-Dmt-Arf 
                 
                   Lys-Dmt-D-Arg-NH 2   
                 
                   Lys-Phe 
                 
                   Lys-Phe-Arg-Dmt 
                 
                   Lys-Phe-NH 2   
                 
                   Lys-Trp-Arg 
                 
                   Lys-Trp-D-Arg-NH 2   
                 
                   Phe-Arg-Dmt-Lys 
                 
                   Phe-Arg-Phe-Lys 
                 
                   Phe-Arg-Phe-Lys 
                 
                   Phe-Arg-Phe-Lys 
                 
                   Phe-Arg-Phe-Lys 
                 
                   Phe-Arg-Phe-Lys 
                 
                   Phe-Arg-Phe-Lys-Glu-Cys-Gly 
                 
                   Phe-Dmt-Arg-Lys 
                 
                   Phe-Lys-Dmt 
                 
                   Phe-Lys-Dmt-NH 2   
                 
                   Succinic monoester CoQ0-Phe-D-Arg-Phe-Lys-NH 2   
                 
                     
                 
             
                
               
               
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
               
            
           
         
       
     
     
         8 . The method of  claim 7 , wherein detecting is performed during administration of the peptide. 
     
     
         9 . The method of  claim 7 , wherein detecting is performed after administration of the peptide. 
     
     
         10 . The method of any one of  claim 7 , wherein detecting comprises HPLC. 
     
     
         11 . The method of  claim 10 , wherein the HPLC comprises reverse phase HPLC. 
     
     
         12 . The method of  claim 10 , wherein the HPLC comprises ion exchange HPLC. 
     
     
         13 . The method of  claim 7 , wherein detecting comprises mass spectrometry. 
     
     
         14 . The method of  claim 7 , wherein the biological sample comprises a fluid. 
     
     
         15 . The method of  claim 7 , wherein the biological sample comprises a cell. 
     
     
         16 . The method of  claim 7 , wherein the biological sample comprises a tissue. 
     
     
         17 . The method of any one of  claims 7 , wherein the biological sample comprises a biopsy. 
     
     
         18 . An aromatic-cationic peptide selected from the group consisting of:
 a) an aromatic-cationic peptide comprising formula VII or a stereoisomer thereof   
       
         
           
           
               
               
           
         
         wherein the chiral centers of formula III are defined as H—(R)-Arg-(S)-DMT-(S)-Lys-(S)-Phe-NH 2 , and wherein stereoisomers are described by the formulas R—S—S—S, S—R—R—R, S—S—S—S, R—R—R—R, R—R—S—S, S—S—R—R, S—R—S—S, R—S—R—R, R—S—R—S, S—R—S—R, R—R—S—R, S—S—R—S, R—R—R—S, S—S—S—R, R—S—S—R, and S—R—R—S; 
         b) an aromatic-cationic peptide comprising formula VII or a constitutional thereof 
       
       
         
           
           
               
               
           
         
         selected from the group consisting of Arg-Dmt-Lys-Phe-NH 2 , Phe-Dmt-Arg-Lys-NH 2 , Phe-Lys-Dmt-Arg-NH 2 , Dmt-Arg-Lys-Phe-NH 2 , Lys-Dmt-Arg-Phe-NH 2 , Phe-Dmt-Lys-Arg-NH 2 , Arg-Lys-Dmt-Phe-NH 2 , or Arg-Dmt-Phe-Lys-NH 2 ; 
         c) an aromatic-cationic peptide comprising formula VIII 
       
       
         
           
           
               
               
           
         
         wherein R is selected from 
         (i) OMe, and 
         (ii) H, 
         d) an aromatic-cationic peptide comprising formula IX 
       
       
         
           
           
               
               
           
         
         wherein R is selected from 
         (i) F, 
         (ii) Cl, and 
         (iii) H, 
         e) an aromatic-cationic peptide comprising formula X 
       
       
         
           
           
               
               
           
         
         wherein R1-R4 are selected from 
         (i) Ac, (ii) H, (iii) H, (iv) H, 
         (i) H, (ii) Ac, (iii) H, (iv) H, 
         (i) H, (ii) H, (iii) Ac, (iv) H, and 
         (i) H, (ii) H, (iii) H, (iv) OH; 
         f) an aromatic-cationic peptide comprising formula XI 
       
       
         
           
           
               
               
           
         
       
     
     
         19 .- 23 . (canceled)

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