AROMATIC-CATIONIC PEPTIDES AND USES OF SAME
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.
1 . An aromatic-cationic peptide selected from the group consisting of:
D -Arg-Tyr-Lys-Phe-NH 2
D -Arg-Dmt- D -Lys-Phe-NH 2
D -Arg-Dmt-Lys- D -Phe-NH 2
Phe- D -Arg- D -Phe-Lys-NH 2
Phe- D -Arg-Phe- D -Lys-NH 2
D -Phe- D -Arg- D -Phe- D -Lys-NH 2
Lys- D -Phe-Arg-Dmt-NH 2
D -Arg-Arg-Dmt-Phe-NH 2
Dmt- D -Phe -Arg-Lys-NH 2
Phe- D -Dmt-Arg-Lys-NH 2
D -Arg-Dmt-Lys-NH 2
Arg- D -Dmt-Lys-NH 2
D -Arg-Dmt-Phe-NH 2
Arg- D -Dmt-Arg-NH 2
Dmt- D -Arg-NH 2
D -Arg-Dmt-NH 2
D -Dmt-Arg-NH 2
Arg- D -Dmt-NH 2
D -Arg- D -Dmt-NH 2
D -Arg- D -Tyr-Lys-Phe-NH 2
D -Arg-Tyr- D -Lys-Phe-NH 2
D -Arg-Tyr-Lys- D -Phe-NH 2
D -Arg- D -Tyr- D -Lys- D -Phe-NH 2
Lys- D -Phe-Arg-Tyr-NH 2
D -Arg-Arg-Tyr-Phe-NH 2
Tyr- D -Phe-Arg-Lys-NH 2
Phe- D -Tyr-Arg-Lys-NH 2
D -Arg-Tyr-Lys-NH 2
Arg- D -Tyr-Lys-NH 2
D -Arg-Tyr-Phe-NH 2
Arg- D -Tyr-Arg-NH 2
Tyr- D -Arg-NH 2
D -Arg-Tyr-NH 2
D -Tyr-Arg-NH 2
Arg- D -Tyr-NH 2
D -Arg- D -Tyr-NH 2
Dmt-Lys-Phe-NH 2
Lys-Dmt- D -Arg-NH 2
Phe-Lys-Dmt-NH 2
D -Arg-Phe-Lys-NH 2
D -Arg-Cha-Lys-NH 2
D -Arg-Trp-Lys-NH 2
Dmt-Lys- D -Phe-NH 2
Dmt-Lys-NH 2
Lys-Phe-NH 2
D -Arg-Cha-Lys-Cha-NH 2
D -Nle-Dmt-Ahe-Phe-NH 2
D -Nle-Cha-Ahe-Cha-NH 2
wherein Cha is cyclohexylalanine, Nle is norleucine, and Ahe is 2-amino-heptanoic acid.
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:
D -Arg-Tyr-Lys-Phe-NH 2
D -Arg-Dmt- D -Lys-Phe-NH 2
D -Arg-Dmt-Lys- D -Phe-NH 2
Phe- D -Arg- D -Phe-Lys-NH 2
Phe- D -Arg-Phe- D -Lys-NH 2
D -Phe- D -Arg- D -Phe- D -Lys-NH 2
Lys- D -Phe-Arg-Dmt-NH 2
D -Arg-Arg-Dmt-Phe-NH 2
Dmt- D -Phe -Arg-Lys-NH 2
Phe- D -Dmt-Arg-Lys-NH 2
D -Arg-Dmt-Lys-NH 2
Arg- D -Dmt-Lys-NH 2
D -Arg-Dmt-Phe-NH 2
Arg- D -Dmt-Arg-NH 2
Dmt- D -Arg-NH 2
D -Arg-Dmt-NH 2
D -Dmt-Arg-NH 2
Arg- D -Dmt-NH 2
D -Arg- D -Dmt-NH 2
D -Arg- D -Tyr-Lys-Phe-NH 2
D -Arg-Tyr- D -Lys-Phe-NH 2
D -Arg-Tyr-Lys- D -Phe-NH 2
D -Arg- D -Tyr- D -Lys- D -Phe-NH 2
Lys- D -Phe-Arg-Tyr-NH 2
D -Arg-Arg-Tyr-Phe-NH 2
Tyr- D -Phe-Arg-Lys-NH 2
Phe- D -Tyr-Arg-Lys-NH 2
D -Arg-Tyr-Lys-NH 2
Arg- D -Tyr-Lys-NH 2
D -Arg-Tyr-Phe-NH 2
Arg- D -Tyr-Arg-NH 2
Tyr- D -Arg-NH 2
D -Arg-Tyr-NH 2
D -Tyr-Arg-NH 2
Arg- D -Tyr-NH 2
D -Arg- D -Tyr-NH 2
Dmt-Lys-Phe-NH 2
Lys-Dmt- D -Arg-NH 2
Phe-Lys-Dmt-NH 2
D -Arg-Phe-Lys-NH 2
D -Arg-Cha-Lys-NH 2
D -Arg-Trp-Lys-NH 2
Dmt-Lys- D -Phe-NH 2
Dmt-Lys-NH 2
Lys-Phe-NH 2
D -Arg-Cha-Lys-Cha-NH 2
D -Nle-Dmt-Ahe-Phe-NH 2
and
D -Nle-Cha-Ahe-Cha-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.