IP Library › Granted Patent US 8,404,646

Granted Patent B2

US 8,404,646 · App. 13/247,648 · Granted Mar 26, 2013

Methods for preventing or treating mitochondrial permeability transition

Inventors: Peter W. Schiller (Montreal, CA); Hazel H. Szeto (New York, NY); Kesheng Zhao (Jackson Heights, NY)

Assignees: Cornell Research Foundation, Inc.; Institut de Recherches Cliniques de Montreal

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Quick Facts

Patent No.: US 8,404,646
App. No.: 13/247,648
Granted: Mar 26, 2013
Kind: B2

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Abstract

The invention provides a method of reducing or preventing mitochondrial permeability transitioning. The method comprises administering an effective amount of an aromatic-cationic peptide having at least one net positive charge; a minimum of four amino acids; a maximum of about twenty amino acids; a relationship between the minimum number of net positive charges (p m ) and the total number of amino acid residues (r) wherein 3 p m is the largest number that is less than or equal to r+1; and a relationship between the minimum number of aromatic groups (a) and the total number of net positive charges (p t ) wherein 2 a is the largest number that is less than or equal to p t +1, except that when a is 1, p t may also be 1.

Claims (645)

1. A method for treating or preventing cytosolic Ca 2+ overload caused by hypoglycemia in a mammal in need thereof, the method comprising administering to the mammal an effective amount of an aromatic-cationic peptide having the amino acid sequence

Lys-D-Arg-Tyr-NH 2 ,

Phe-D-Arg-His,

D-Tyr-Trp-Lys-NH 2 ,

Trp-D-Lys-Tyr-Arg-NH 2 ,

Tyr-His-D-Gly-Met,

Phe-Arg-D-His-Asp,

Tyr-D-Arg-Phe-Lys-Glu-NH 2 ,

Met-Tyr-D-Lys-Phe-Arg,

D-His-Glu-Lys-Tyr-D-Phe-Arg,

Lys-D-Gln-Tyr-Arg-D-Phe-Trp-NH 2 ,

Phe-D-Arg-Lys-Trp-Tyr-D-Arg-His,

Gly-D-Phe-Lys-Tyr-His-D-Arg-Tyr-NH 2 ,

Val-D-Lys-His-Tyr-D-Phe-Ser-Tyr-Arg-NH 2 ,

Trp-Lys-Phe-D-Asp-Arg-Tyr-D-His-Lys,

Lys-Trp-D-Tyr-Arg-Asn-Phe-Tyr-D-His-NH 2 ,

Thr-Gly-Tyr-Arg-D-His-Phe-Trp-D-His-Lys,

Asp-D-Trp-Lys-Tyr-D-His-Phe-Arg-D-Gly-Lys-NH 2 ,

D-His-Lys-Tyr-D-Phe-Glu-D-Asp-D-His-D-Lys-Arg-Trp-

NH 2 ,

Ala-D-Phe-D-Arg-Tyr-Lys-D-Trp-His-D-Tyr-Gly-Phe,

Tyr-D-His-Phe-D-Arg-Asp-Lys-D-Arg-His-Trp-D-His-

Phe,

Phe-Phe-D-Tyr-Arg-Glu-Asp-D-Lys-Arg-D-Arg-His-Phe-

NH 2 ,

Phe-Try-Lys-D-Arg-Trp-His-D-Lys-D-Lys-Glu-Arg-D-

Tyr-Thr,

Tyr-Asp-D-Lys-Tyr-Phe-D-Lys-D-Arg-Phe-Pro-D-Tyr-

His-Lys Glu-Arg-D-Lys-Tyr-D-Val-Phe-D-His-Trp-Arg-

D-Gly-Tyr-Arg-D-Met-NH 2 ,

Arg-D-Leu-D-Tyr-Phe-Lys-Glu-D-Lys-Arg-D-Trp-Lys-D-

Phe-Tyr-D-Arg-Gly,

D-Glu-Asp-Lys-D-Arg-D-His-Phe-Phe-D-V al-Tyr-Arg-

Tyr-D-Tyr-Arg-His-Phe-NH 2 ,

Asp-Arg-D-Phe-Cys-Phe-D-Arg-D-Lys-Tyr-Arg-D-Tyr-

Trp-D-His-Tyr-D-Phe-Lys-Phe,

His-Tyr-D-Arg-Trp-Lys-Phe-D-Asp-Ala-Arg-Cys-D-Tyr-

His-Phe-D-Lys-Tyr-His-Ser-NH 2 ,

Gly-Ala-Lys-Phe-D-Lys-Glu-Arg-Tyr-His-D-Arg-D-Arg-

Asp-Tyr-Trp-D-His-Trp-His-D-Lys-Asp,

Thr-Tyr-Arg-D-Lys-Trp-Tyr-Glu-Asp-D-Lys-D-Arg-His-

Phe-D-Tyr-Gly-Val-Ile-D-His-Arg-Tyr-Lys-NH 2 ,

Tyr-D-Arg-Phe-Lys-NH 2 ,

Tyr-D-Arg-Phe-Orn-NH 2 ,

Tyr-D-Arg-Phe-Dab-NH 2 ,

Tyr-D-Arg-Phe-Dap-NH 2 ,

2′6′Dmt-D-Arg-Phe-Lys-NH 2 ,

2′6′Dmt-D-Arg-Phe-Lys-Cys-NH 2 ,

2′6′Dmt-D-Arg-Phe-Lys-NH(CH 2 ) 2 -NH-dns-NH 2 ,

2′6′Dmt-D-Arg-Phe-Lys-NH(CH 2 ) 2 -NH-atn-NH 2 ,

2′6′Dmt-D-Arg-Phe-dnsLys-NH 2 ,

2′6′Dmt-D-Cit-Phe-Lys-NH 2 ,

2′6′Dmt-D-Cit-Phe-Ahp-NH 2 ,

2′6′Dmt-D-Arg-Phe-Orn-NH 2

2′6′Dmt-D-Arg-Phe-Dab-NH 2 ,

2′6′Dmt-D-Arg-Phe-Dap-NH 2 ,

2′6′Dmt-D-Arg-Phe-Ahp(2-aminoheptanoic acid)-NH 2 ,

Bio-2′6′Dmt-D-Arg-Phe-Lys-NH 2 ,

3′5′Dmt-D-Arg-Phe-Lys-NH 2 ,

3′5′Dmt-D-Arg-Phe-Orn-NH 2 ,

3′5′Dmt-D-Arg-Phe-Dab-NH 2 ,

3′5′Dmt-D-Arg-Phe-Dap-NH 2 ,

Tyr-D-Arg-Tyr-Lys-NH 2 ,

Tyr-D-Arg-Tyr-Orn-NH 2 ,

Tyr-D-Arg-Tyr-Dab-NH 2 ,

Tyr-D-Arg-Tyr-Dap-NH 2 ,

2′6′Dmt-D-Arg-Tyr-Lys-NH 2 ,

2′6′Dmt-D-Arg-Tyr-Orn-NH 2 ,

2′6′Dmt-D-Arg-Tyr-Dab-NH 2 ,

2′6′Dmt-D-Arg-Tyr-Dap-NH 2 ,

2′6′Dmt-D-Arg-2′6′Dmt-Lys-NH 2 ,

2′6′Dmt-D-Arg-2′6′Dmt-Orn-NH 2 ,

2′6′Dmt-D-Arg-2′6′Dmt-Dab-NH 2 ,

2′6′Dmt-D-Arg-2′6′Dmt-Dap-NH 2 ,

3′5Dmt-D-Arg-3′5Dmt-Arg-NH 2 ,

3′5Dmt-D-Arg-3′5Dmt-Lys-NH 2 ,

3′5Dmt-D-Arg-3′5Dmt-Orn-NH 2 ,

3′5Dmt-D-Arg-3′5Dmt-Dab-NH 2 ,

Tyr-D-Lys-Phe-Dap-NH 2 ,

Tyr-D-Lys-Phe-Arg-NH 2 ,

Tyr-D-Lys-Phe-Lys-NH 2 ,

Tyr-D-Lys-Phe-Orn-NH 2 ,

2′6′Dmt-D-Lys-Phe-Dab-NH 2

2′6′Dmt-D-Lys-Phe-Dap-NH 2 ,

2′6′Dmt-D-Lys-Phe-Arg-NH 2 ,

2′6′Dmt-D-Lys-Phe-Lys-NH 2 ,

3′5′Dmt-D-Lys-Phe-Orn-NH 2 ,

3′5′Dmt-D-Lys-Phe-Dab-NH 2 ,

3′5′Dmt-D-Lys-Phe-Dap-NH 2 ,

3′5′Dmt-D-Lys-Phe-Arg-NH 2 ,

Tyr-D-Lys-Tyr-Lys-NH 2 ,

Tyr-D-Lys-Tyr-Orn-NH 2 ,

Tyr-D-Lys-Tyr-Dab-NH 2 ,

Tyr-D-Lys-Tyr-Dap-NH 2 ,

2′6′Dmt-D-Lys-Tyr-Lys-NH 2 ,

2′6′Dmt-D-Lys-Tyr-Orn-NH 2 ,

2′6′Dmt-D-Lys-Tyr-Dab-NH 2 ,

2′6′Dmt-D-Lys-Tyr-Dap-NH 2 ,

2′6′Dmt-D-Lys-2′6′Dmt-Lys-NH 2 ,

2′6′Dmt-D-Lys-2′6′Dmt-Orn-NH 2 ,

2 6′Dmt-D-Lys-2′6′Dmt-Dab-NH 2 ,

2′6′Dmt-D-Lys-2′6′Dmt-Dap-NH 2 ,

2′6′Dmt-D-Arg-Phe-dnsDap-NH 2 ,

2′6′Dmt-D-Arg-Phe-atnDap-NH 2 ,

3′5′Dmt-D-Lys-3′5′Dmt-Lys-NH 2 ,

3′5′Dmt-D-Lys-3′5′Dmt-Orn-NH 2 ,

3′5′Dmt-D-Lys-3′5′Dmt-Dab-NH 2 ,

3′5′Dmt-D-Lys-3′5′Dmt-Dap-NH 2 ,

Tyr-D-Lys-Phe-Arg-NH 2 ,

Tyr-D-Orn-Phe-Arg-NH 2 ,

Tyr-D-Dab-Phe-Arg-NH 2 ,

Tyr-D-Dap-Phe-Arg-NH 2 ,

2′6′Dmt-D-Arg-Phe-Arg-NH 2 ,

2′6′Dmt-D-Lys-Phe-Arg-NH 2 ,

2′6′Dmt-D-Orn-Phe-Arg-NH 2 ,

2′6′Dmt-D-Dab-Phe-Arg-NH 2 ,

3′5′Dmt-D-Dap-Phe-Arg-NH 2 ,

3′5′Dmt-D-Arg-Phe-Arg-NH 2 ,

3′5′Dmt-D-Lys-Phe-Arg-NH 2 ,

3′5′Dmt-D-Orn-Phe-Arg-NH 2 ,

Tyr-D-Lys-Tyr-Arg-NH 2 ,

Tyr-D-Orn-Tyr-Arg-NH 2 ,

Tyr-D-Dab-Tyr-Arg-NH 2 ,

Tyr-D-Dap-Tyr-Arg-NH 2 ,

2′6′Dmt-D-Arg-2′6′Dmt-Arg-NH 2 ,

2′6′Dmt-D-Lys-2′6′Dmt-Arg-NH 2 ,

2′6′Dmt-D-Orn-2′6′Dmt-Arg-NH 2 ,

2′6′Dmt-D-Dab-2′6′Dmt-Arg-NH 2 ,

3′5′Dmt-D-Dap-3′5′Dmt-Arg-NH 2 ,

3′5′Dmt-D-Arg-3′5′Dmt-Arg-NH 2 ,

3′5′Dmt-D-Lys-3′5′Dmt-Arg-NH 2 ,

3′5′Dmt-D-Orn-3′5′Dmt-Arg-NH 2 ,

Mmt-D-Arg-Phe-Lys-NH 2 ,

Mmt-D-Arg-Phe-Orn-NH 2 ,

Mmt-D-Arg-Phe-Dab-NH 2 ,

Mmt-D-Arg-Phe-Dap-NH 2 ,

Tmt-D-Arg-Phe-Lys-NH 2 ,

Tmt-D-Arg-Phe-Orn-NH 2 ,

Tmt-D-Arg-Phe-Dab-NH 2 ,

Tmt-D-Arg-Phe-Dap-NH 2 ,

Hmt-D-Arg-Phe-Lys-NH 2 ,

Hmt-D-Arg-Phe-Orn-NH 2 ,

Hmt-D-Arg-Phe-Dab-NH 2 ,

Hmt-D-Arg-Phe-Dap-NH 2 ,

Mmt-D-Lys-Phe-Lys-NH 2 ,

Mmt-D-Lys-Phe-Orn-NH 2 ,

Mmt-D-Lys-Phe-Dab-NH 2 ,

Mmt-D-Lys-Phe-Dap-NH 2 ,

Mmt-D-Lys-Phe-Arg-NH 2 ,

Tmt-D-Lys-Phe-Lys-NH 2 ,

Tmt-D-Lys-Phe-Orn-NH 2 ,

Tmt-D-Lys-Phe-Dab-NH 2 ,

Tmt-D-Lys-Phe-Dap-NH 2 ,

Tmt-D-Lys-Phe-Arg-NH 2 ,

Hmt-D-Lys-Phe-Lys-NH 2 ,

Hmt-D-Lys-Phe-Orn-NH 2 ,

Hmt-D-Lys-Phe-Dab-NH 2 ,

Hmt-D-Lys-Phe-Dap-NH 2 ,

Hmt-D-Lys-Phe-Arg-NH 2 ,

Mmt-D-Lys-Phe-Arg-NH 2 ,

Mmt-D-Orn-Phe-Arg-NH 2 ,

Mmt-D-Dab-Phe-Arg-NH 2 ,

Mmt-D-Dap-Phe-Arg-NH 2 ,

Mmt-D-Arg-Phe-Arg-NH 2 ,

Tmt-D-Lys-Phe-Arg-NH 2 ,

Tmt-D-Orn-Phe-Arg-NH 2 ,

Tmt-D-Dab-Phe-Arg-NH 2 ,

Tmt-D-Dap-Phe-Arg-NH 2 ,

Tmt-D-Arg-Phe-Arg-NH 2 ,

Hmt-D-Lys-Phe-Arg-NH 2

Hmt-D-Orn-Phe-Arg-NH 2 ,

Hmt-D-Dab-Phe-Arg-NH 2 ,

Hmt-D-Dap-Phe-Arg-NH 2 ,

Hmt-D-Arg-Phe-Arg-NH 2 ,

D-Arg-2′6′Dmt-Lys-Phe-NH 2 ,

D-Arg-2′6′Dmt-Phe-Lys-NH 2 ,

D-Arg-Phe-Lys-2′6′Dmt-NH 2 ,

D-Arg-Phe-2′6′Dmt-Lys-NH 2 ,

D-Arg-Lys-2′6′Dmt-Phe-NH 2 ,

D-Arg-Lys-Phe-2′6′Dmt-NH 2 ,

Phe-Lys-2′6′Dmt-D-Arg-NH 2 ,

Phe-Lys-D-Arg-2′6′Dmt-NH 2 ,

Phe-D-Arg-2′6′Dmt-Lys-NH 2 ,

Phe-D-Arg-Lys-2′6′Dmt-NH 2 ,

Phe-2′6′Dmt-D-Arg-Lys-NH 2 ,

Phe-2′6′Dmt-Lys-D-Arg-NH 2 ,

Lys-Phe-D-Arg-2′6′Dmt-NH 2 ,

Lys-Phe-2′6′Dmt-D-Arg-NH 2 ,

Lys-2′6′Dmt-D-Arg-Phe-NH 2 ,

Lys-2′6′Dmt-Phe-D-Arg-NH 2 ,

Lys-D-Arg-Phe-2′6′Dmt-NH 2 ,

Lys-D-Arg-2′6′Dmt-Phe-NH 2 ,

D-Arg-2′6′Dmt-D-Arg-Phe-NH 2 ,

D-Arg-2′6′Dmt-D-Arg-2′6′Dmt-NH 2 ,

D-Arg-2′6′Dmt-D-Arg-Tyr-NH 2 ,

D-Arg-2′6′Dmt-D-Arg-Trp-NH 2 ,

Trp-D-Arg-Phe-Lys-NH 2 ,

Trp-D-Arg-Tyr-Lys-NH 2 ,

Trp-D-Arg-Trp-Lys-NH 2 ,

Trp-D-Arg-2′6′Dmt-Lys-NH 2

D-Arg-Trp-Lys-Phe-NH 2 ,

D-Arg-Trp-Phe-Lys-NH 2 ,

D-Arg-Trp-Lys-2′6′Dmt-NH 2

D-Arg-Trp-2′6′Dmt-Lys-NH 2 ,

D-Arg-Lys-Trp-Phe-NH 2 ,

D-Arg-Lys-Trp-2′6′Dmt-NH 2 ,

Cha-D-Arg-Phe-Lys-NH 2 ,

Ala-D-Arg-Phe-Lys-NH 2 .

2. The method of claim 1 , wherein the mammal is a human.

3. The method of claim 1 , wherein the peptide is administered orally, topically, intranasally, systemically, intravenously, subcutaneously, intramuscularly, intrathecally, or transdermally.

4. The method of claim 1 , wherein the peptide is combined with a pharmaceutically acceptable carrier prior to administration to the mammal.

5. The method of claim 1 , wherein the peptide has the amino acid sequence D-Arg-2′6′Dmt-Lys-Phe-NH 2 .

6. The method of claim 1 , wherein the peptide has the amino acid sequence 2′6′Dmt-D-Arg-Phe-Lys-NH 2 .

7. The method of claim 1 , wherein the peptide has the amino acid sequence Phe-D-Arg-Phe-Lys-NH 2 .

8. A method for preventing Ca 2+ -induced necrotic cell death caused by hypoglycemia in a mammal in need thereof, the method comprising administering to the mammal an effective amount of an aromatic-cationic peptide having the amino acid sequence

Lys-D-Arg-Tyr-NH 2 ,

Phe-D-Arg-His,

D-Tyr-Trp-Lys-NH 2 ,

Trp-D-Lys-Tyr-Arg-NH 2 ,

Tyr-His-D-Gly-Met,

Phe-Arg-D-His-Asp,

Tyr-D-Arg-Phe-Lys-Glu-NH 2 ,

Met-Tyr-D-Lys-Phe-Arg,

D-His-Glu-Lys-Tyr-D-Phe-Arg,

Lys-D-Gln-Tyr-Arg-D-Phe-Trp-NH 2 ,

Phe-D-Arg-Lys-Trp-Tyr-D-Arg-His,

Gly-D-Phe-Lys-Tyr-His-D-Arg-Tyr-NH 2 ,

Val-D-Lys-His-Tyr-D-Phe-Ser-Tyr-Arg-NH 2 ,

Trp-Lys-Phe-D-Asp-Arg-Tyr-D-His-Lys,

Lys-Trp-D-Tyr-Arg-Asn-Phe-Tyr-D-His-NH 2 ,

Thr-Gly-Tyr-Arg-D-His-Phe-Trp-D-His-Lys,

Asp-D-Trp-Lys-Tyr-D-His-Phe-Arg-D-Gly-Lys-NH 2 ,

D-His-Lys-Tyr-D-Phe-Glu-D-Asp-D-His-D-Lys-Arg-Trp-

NH 2 ,

Ala-D-Phe-D-Arg-Tyr-Lys-D-Trp-His-D-Tyr-Gly-Phe,

Tyr-D-His-Phe-D-Arg-Asp-Lys-D-Arg-His-Trp-D-His-

Phe,

Phe-Phe-D-Tyr-Arg-Glu-Asp-D-Lys-Arg-D-Arg-His-Phe-

NH 2 ,

Phe-Try-Lys-D-Arg-Trp-His-D-Lys-D-Lys-Glu-Arg-D-

Tyr-Thr,

Tyr-Asp-D-Lys-Tyr-Phe-D-Lys-D-Arg-Phe-Pro-D-Tyr-

His-Lys Glu-Arg-D-Lys-Tyr-D-Val-Phe-D-His-Trp-Arg-

D-Gly-Tyr-Arg-D-Met-NH 2 ,

Arg-D-Leu-D-Tyr-Phe-Lys-Glu-D-Lys-Arg-D-Trp-Lys-D-

Phe-Tyr-D-Arg-Gly,

D-Glu-Asp-Lys-D-Arg-D-His-Phe-Phe-D-V al-Tyr-Arg-

Tyr-D-Tyr-Arg-His-Phe-NH 2 ,

Asp-Arg-D-Phe-Cys-Phe-D-Arg-D-Lys-Tyr-Arg-D-Tyr-

Trp-D-His-Tyr-D-Phe-Lys-Phe,

His-Tyr-D-Arg-Trp-Lys-Phe-D-Asp-Ala-Arg-Cys-D-Tyr-

His-Phe-D-Lys-Tyr-His-Ser-NH 2 ,

Gly-Ala-Lys-Phe-D-Lys-Glu-Arg-Tyr-His-D-Arg-D-Arg-

Asp-Tyr-Trp-D-His-Trp-His-D-Lys-Asp,

Thr-Tyr-Arg-D-Lys-Trp-Tyr-Glu-Asp-D-Lys-D-Arg-His-

Phe-D-Tyr-Gly-Val-Ile-D-His-Arg-Tyr-Lys-NH 2 ,

Tyr-D-Arg-Phe-Lys-NH 2 ,

Tyr-D-Arg-Phe-Orn-NH 2 ,

Tyr-D-Arg-Phe-Dab-NH 2 ,

Tyr-D-Arg-Phe-Dap-NH 2 ,

2′6′Dmt-D-Arg-Phe-Lys-NH 2 ,

2′6′Dmt-D-Arg-Phe-Lys-Cys-NH 2 ,

2′6′Dmt-D-Arg-Phe-Lys-NH(CH 2 ) 2 -NH-dns-NH 2 ,

2′6′Dmt-D-Arg-Phe-Lys-NH(CH 2 ) 2 -NH-atn-NH 2 ,

2′6′Dmt-D-Arg-Phe-dnsLys-NH 2 ,

2′6′Dmt-D-Cit-Phe-Lys-NH 2 ,

2′6′Dmt-D-Cit-Phe-Ahp-NH 2 ,

2′6′Dmt-D-Arg-Phe-Orn-NH 2

2′6′Dmt-D-Arg-Phe-Dab-NH 2 ,

2′6′Dmt-D-Arg-Phe-Dap-NH 2 ,

2′6′Dmt-D-Arg-Phe-Ahp(2-aminoheptanoic acid)-NH 2 ,

Bio-2′6′Dmt-D-Arg-Phe-Lys-NH 2 ,

3′5′Dmt-D-Arg-Phe-Lys-NH 2 ,

3′5′Dmt-D-Arg-Phe-Orn-NH 2 ,

3′5′Dmt-D-Arg-Phe-Dab-NH 2 ,

3′5′Dmt-D-Arg-Phe-Dap-NH 2 ,

Tyr-D-Arg-Tyr-Lys-NH 2 ,

Tyr-D-Arg-Tyr-Orn-NH 2 ,

Tyr-D-Arg-Tyr-Dab-NH 2 ,

Tyr-D-Arg-Tyr-Dap-NH 2 ,

2′6′Dmt-D-Arg-Tyr-Lys-NH 2 ,

2′6′Dmt-D-Arg-Tyr-Orn-NH 2 ,

2′6′Dmt-D-Arg-Tyr-Dab-NH 2 ,

2′6′Dmt-D-Arg-Tyr-Dap-NH 2 ,

2′6′Dmt-D-Arg-2′6′Dmt-Lys-NH 2 ,

2′6′Dmt-D-Arg-2′6′Dmt-Orn-NH 2 ,

2′6′Dmt-D-Arg-2′6′Dmt-Dab-NH 2 ,

2′6′Dmt-D-Arg-2′6′Dmt-Dap-NH 2 ,

3′5Dmt-D-Arg-3′5Dmt-Arg-NH 2 ,

3′5Dmt-D-Arg-3′5Dmt-Lys-NH 2 ,

3′5Dmt-D-Arg-3′5Dmt-Orn-NH 2 ,

3′5Dmt-D-Arg-3′5Dmt-Dab-NH 2 ,

Tyr-D-Lys-Phe-Dap-NH 2 ,

Tyr-D-Lys-Phe-Arg-NH 2 ,

Tyr-D-Lys-Phe-Lys-NH 2 ,

Tyr-D-Lys-Phe-Orn-NH 2 ,

2′6′Dmt-D-Lys-Phe-Dab-NH 2

2′6′Dmt-D-Lys-Phe-Dap-NH 2 ,

2′6′Dmt-D-Lys-Phe-Arg-NH 2 ,

2′6′Dmt-D-Lys-Phe-Lys-NH 2 ,

3′5′Dmt-D-Lys-Phe-Orn-NH 2 ,

3′5′Dmt-D-Lys-Phe-Dab-NH 2 ,

3′5′Dmt-D-Lys-Phe-Dap-NH 2 ,

3′5′Dmt-D-Lys-Phe-Arg-NH 2 ,

Tyr-D-Lys-Tyr-Lys-NH 2 ,

Tyr-D-Lys-Tyr-Orn-NH 2 ,

Tyr-D-Lys-Tyr-Dab-NH 2 ,

Tyr-D-Lys-Tyr-Dap-NH 2 ,

2′6′Dmt-D-Lys-Tyr-Lys-NH 2 ,

2′6′Dmt-D-Lys-Tyr-Orn-NH 2 ,

2′6′Dmt-D-Lys-Tyr-Dab-NH 2 ,

2′6′Dmt-D-Lys-Tyr-Dap-NH 2 ,

2′6′Dmt-D-Lys-2′6′Dmt-Lys-NH 2 ,

2′6′Dmt-D-Lys-2′6′Dmt-Orn-NH 2 ,

2′6′Dmt-D-Lys-2′6′Dmt-Dab-NH 2 ,

2′6′Dmt-D-Lys-2′6′Dmt-Dap-NH 2 ,

2′6′Dmt-D-Arg-Phe-dnsDap-NH 2 ,

2′6′Dmt-D-Arg-Phe-atnDap-NH 2 ,

3′5′Dmt-D-Lys-3′5′Dmt-Lys-NH 2 ,

3′5′Dmt-D-Lys-3′5′Dmt-Orn-NH 2 ,

3′5′Dmt-D-Lys-3′5′Dmt-Dab-NH 2 ,

3′5′Dmt-D-Lys-3′5′Dmt-Dap-NH 2 ,

Tyr-D-Lys-Phe-Arg-NH 2 ,

Tyr-D-Orn-Phe-Arg-NH 2 ,

Tyr-D-Dab-Phe-Arg-NH 2 ,

Tyr-D-Dap-Phe-Arg-NH 2 ,

2′6′Dmt-D-Arg-Phe-Arg-NH 2 ,

2′6′Dmt-D-Lys-Phe-Arg-NH 2 ,

2′6′Dmt-D-Orn-Phe-Arg-NH 2 ,

2′6′Dmt-D-Dab-Phe-Arg-NH 2 ,

3′5′Dmt-D-Dap-Phe-Arg-NH 2 ,

3′5′Dmt-D-Arg-Phe-Arg-NH 2 ,

3′5′Dmt-D-Lys-Phe-Arg-NH 2 ,

3′5′Dmt-D-Orn-Phe-Arg-NH 2 ,

Tyr-D-Lys-Tyr-Arg-NH 2 ,

Tyr-D-Orn-Tyr-Arg-NH 2 ,

Tyr-D-Dab-Tyr-Arg-NH 2 ,

Tyr-D-Dap-Tyr-Arg-NH 2 ,

2′6′Dmt-D-Arg-2′6′Dmt-Arg-NH 2 ,

2′6′Dmt-D-Lys-2′6′Dmt-Arg-NH 2 ,

2′6′Dmt-D-Orn-2′6′Dmt-Arg-NH 2 ,

2′6′Dmt-D-Dab-2′6′Dmt-Arg-NH 2 ,

3′5′Dmt-D-Dap-3′5′Dmt-Arg-NH 2 ,

3′5′Dmt-D-Arg-3′5′Dmt-Arg-NH 2 ,

3′5′Dmt-D-Lys-3′5′Dmt-Arg-NH 2 ,

3′5′Dmt-D-Orn-3′5′Dmt-Arg-NH 2 ,

Mmt-D-Arg-Phe-Lys-NH 2 ,

Mmt-D-Arg-Phe-Orn-NH 2 ,

Mmt-D-Arg-Phe-Dab-NH 2 ,

Mmt-D-Arg-Phe-Dap-NH 2 ,

Tmt-D-Arg-Phe-Lys-NH 2 ,

Tmt-D-Arg-Phe-Orn-NH 2 ,

Tmt-D-Arg-Phe-Dab-NH 2 ,

Tmt-D-Arg-Phe-Dap-NH 2 ,

Hmt-D-Arg-Phe-Lys-NH 2 ,

Hmt-D-Arg-Phe-Orn-NH 2 ,

Hmt-D-Arg-Phe-Dab-NH 2 ,

Hmt-D-Arg-Phe-Dap-NH 2 ,

Mmt-D-Lys-Phe-Lys-NH 2 ,

Mmt-D-Lys-Phe-Orn-NH 2 ,

Mmt-D-Lys-Phe-Dab-NH 2 ,

Mmt-D-Lys-Phe-Dap-NH 2 ,

Mmt-D-Lys-Phe-Arg-NH 2 ,

Tmt-D-Lys-Phe-Lys-NH 2 ,

Tmt-D-Lys-Phe-Orn-NH 2 ,

Tmt-D-Lys-Phe-Dab-NH 2 ,

Tmt-D-Lys-Phe-Dap-NH 2 ,

Tmt-D-Lys-Phe-Arg-NH 2 ,

Hmt-D-Lys-Phe-Lys-NH 2 ,

Hmt-D-Lys-Phe-Orn-NH 2 ,

Hmt-D-Lys-Phe-Dab-NH 2 ,

Hmt-D-Lys-Phe-Dap-NH 2 ,

Hmt-D-Lys-Phe-Arg-NH 2 ,

Mmt-D-Lys-Phe-Arg-NH 2 ,

Mmt-D-Orn-Phe-Arg-NH 2 ,

Mmt-D-Dab-Phe-Arg-NH 2 ,

Mmt-D-Dap-Phe-Arg-NH 2 ,

Mmt-D-Arg-Phe-Arg-NH 2 ,

Tmt-D-Lys-Phe-Arg-NH 2 ,

Tmt-D-Orn-Phe-Arg-NH 2 ,

Tmt-D-Dab-Phe-Arg-NH 2 ,

Tmt-D-Dap-Phe-Arg-NH 2 ,

Tmt-D-Arg-Phe-Arg-NH 2 ,

Hmt-D-Lys-Phe-Arg-NH 2

Hmt-D-Orn-Phe-Arg-NH 2 ,

Hmt-D-Dab-Phe-Arg-NH 2 ,

Hmt-D-Dap-Phe-Arg-NH 2 ,

Hmt-D-Arg-Phe-Arg-NH 2 ,

D-Arg-2′6′Dmt-Lys-Phe-NH 2 ,

D-Arg-2′6′Dmt-Phe-Lys-NH 2 ,

D-Arg-Phe-Lys-2′6′Dmt-NH 2 ,

D-Arg-Phe-2′6′Dmt-Lys-NH 2 ,

D-Arg-Lys-2′6′Dmt-Phe-NH 2 ,

D-Arg-Lys-Phe-2′6′Dmt-NH 2 ,

Phe-Lys-2′6′Dmt-D-Arg-NH 2 ,

Phe-Lys-D-Arg-2′6′Dmt-NH 2 ,

Phe-D-Arg-2′6′Dmt-Lys-NH 2 ,

Phe-D-Arg-Lys-2′6′Dmt-NH 2 ,

Phe-2′6′Dmt-D-Arg-Lys-NH 2 ,

Phe-2′6′Dmt-Lys-D-Arg-NH 2 ,

Lys-Phe-D-Arg-2′6′Dmt-NH 2 ,

Lys-Phe-2′6′Dmt-D-Arg-NH 2 ,

Lys-2′6′Dmt-D-Arg-Phe-NH 2 ,

Lys-2′6′Dmt-Phe-D-Arg-NH 2 ,

Lys-D-Arg-Phe-2′6′Dmt-NH 2 ,

Lys-D-Arg-2′6′Dmt-Phe-NH 2 ,

D-Arg-2′6′Dmt-D-Arg-Phe-NH 2 ,

D-Arg-2′6′Dmt-D-Arg-2′6′Dmt-NH 2 ,

D-Arg-2′6′Dmt-D-Arg-Tyr-NH 2 ,

D-Arg-2′6′Dmt-D-Arg-Trp-NH 2 ,

Trp-D-Arg-Phe-Lys-NH 2 ,

Trp-D-Arg-Tyr-Lys-NH 2 ,

Trp-D-Arg-Trp-Lys-NH 2 ,

Trp-D-Arg-2′6′Dmt-Lys-NH 2

D-Arg-Trp-Lys-Phe-NH 2 ,

D-Arg-Trp-Phe-Lys-NH 2 ,

D-Arg-Trp-Lys-2′6′Dmt-NH 2

D-Arg-Trp-2′6′Dmt-Lys-NH 2 ,

D-Arg-Lys-Trp-Phe-NH 2 ,

D-Arg-Lys-Trp-2′6′Dmt-NH 2 ,

Cha-D-Arg-Phe-Lys-NH 2 ,

Ala-D-Arg-Phe-Lys-NH 2 .

9. The method of claim 8 , wherein the mammal is a human.

10. The method of claim 8 , wherein the peptide is administered orally, topically, intranasally, systemically, intravenously, subcutaneously, intramuscularly, intrathecally, or transdermally.

11. The method of claim 8 , wherein the peptide is combined with a pharmaceutically acceptable carrier prior to administration to the mammal.

12. The method of claim 8 , wherein the peptide has the amino acid sequence D-Arg-2′6′Dmt-Lys-Phe-NH 2 .

13. The method of claim 8 , wherein the peptide has the amino acid sequence 2′6′Dmt-D-Arg-Phe-Lys-NH 2 .

14. The method of claim 8 , wherein the peptide has the amino acid sequence Phe-D-Arg-Phe-Lys-NH 2 .

15. A method of regulating cytosolic Ca 2+ levels in hypoglycemia in a mammal in need thereof, the method comprising administering to the mammal an effective amount of an aromatic-cationic peptide having the amino acid sequence

Lys-D-Arg-Tyr-NH 2 ,

Phe-D-Arg-His,

D-Tyr-Trp-Lys-NH 2 ,

Trp-D-Lys-Tyr-Arg-NH 2 ,

Tyr-His-D-Gly-Met,

Phe-Arg-D-His-Asp,

Tyr-D-Arg-Phe-Lys-Glu-NH 2 ,

Met-Tyr-D-Lys-Phe-Arg,

D-His-Glu-Lys-Tyr-D-Phe-Arg,

Lys-D-Gln-Tyr-Arg-D-Phe-Trp-NH 2 ,

Phe-D-Arg-I.ys-Trp-Tyr-D-Arg-His,

Gly-D-Phe-Lys-Tyr-His-D-Arg-Tyr-NH 2 ,

Val-D-Lys-His-Tyr-D-Phe-Ser-Tyr-Arg-NH 2 ,

Trp-Lys-Phe-D-Asp-Arg-Tyr-D-His-Lys,

Lys-Trp-D-Tyr-Arg-Asn-Phe-Tyr-D-His-NH 2 ,

Thr-Gly-Tyr-Arg-D-His-Phe-Trp-D-His-Lys,

Asp-D-Trp-Lys-Tyr-D-His-Phe-Arg-D-Gly-Lys-NH 2 ,

D-His-Lys-Tyr-D-Phe-Glu-D-Asp-D-His-D-Lys-Arg-Trp-

NH 2 ,

Ala-D-Phe-D-Arg-Tyr-Lys-D-Trp-His-D-Tyr-Gly-Phe,

Tyr-D-His-Phe-D-Arg-Asp-Lys-D-Arg-His-Trp-D-His-

Phe,

Phe-Phe-D-Tyr-Arg-Glu-Asp-D-Lys-Arg-D-Arg-His-Phe-

NH 2 ,

Phe-Try-Lys-D-Arg-Trp-His-D-Lys-D-Lys-Glu-Arg-D-

Tyr-Thr,

Tyr-Asp-D-Lys-Tyr-Phe-D-Lys-D-Arg-Phe-Pro-D-Tyr-

His-Lys Glu-Arg-D-Lys-Tyr-D-Val-Phe-D-His-Trp-Arg-

D-Gly-Tyr-Arg-D-Met-NH 2 ,

Arg-D-Leu-D-Tyr-Phe-Lys-Glu-D-Lys-Arg-D-Trp-Lys-D-

Phe-Tyr-D-Arg-Gly,

D-Glu-Asp-Lys-D-Arg-D-His-Phe-Phe-D-V al-Tyr-Arg-

Tyr-D-Tyr-Arg-His-Phe-NH 2 ,

Asp-Arg-D-Phe-Cys-Phe-D-Arg-D-Lys-Tyr-Arg-D-Tyr-

Trp-D-His-Tyr-D-Phe-Lys-Phe,

His-Tyr-D-Arg-Trp-Lys-Phe-D-Asp-Ala-Arg-Cys-D-Tyr-

His-Phe-D-Lys-Tyr-His-Ser-NH 2 ,

Gly-Ala-Lys-Phe-D-Lys-Glu-Arg-Tyr-His-D-Arg-D-Arg-

Asp-Tyr-Trp-D-His-Trp-His-D-Lys-Asp,

Thr-Tyr-Arg-D-Lys-Trp-Tyr-Glu-Asp-D-Lys-D-Arg-His-

Phe-D-Tyr-Gly-Val-Ile-D-His-Arg-Tyr-Lys-NH 2 ,

Tyr-D-Arg-Phe-Lys-NH 2 ,

Tyr-D-Arg-Phe-Orn-NH 2 ,

Tyr-D-Arg-Phe-Dab-NH 2 ,

Tyr-D-Arg-Phe-Dap-NH 2 ,

2′6′Dmt-D-Arg-Phe-Lys-NH 2 ,

2′6′Dmt-D-Arg-Phe-Lys-Cys-NH 2 ,

2′6′Dmt-D-Arg-Phe-Lys-NH(CH 2 ) 2 -NH-dns-NH 2 ,

2′6′Dmt-D-Arg-Phe-Lys-NH(CH 2 ) 2 -NH-atn-NH 2 ,

2′6′Dmt-D-Arg-Phe-dnsLys-NH 2 ,

2′6′Dmt-D-Cit-Phe-Lys-NH 2 ,

2′6′Dmt-D-Cit-Phe-Ahp-NH 2 ,

2′6′Dmt-D-Arg-Phe-Orn-NH 2

2′6′Dmt-D-Arg-Phe-Dab-NH 2 ,

2′6′Dmt-D-Arg-Phe-Dap-NH 2 ,

2′6′Dmt-D-Arg-Phe-Ahp(2-aminoheptanoic acid)-NH 2 ,

Bio-2′6′Dmt-D-Arg-Phe-Lys-NH 2 ,

3′5′Dmt-D-Arg-Phe-Lys-NH 2 ,

3′5′Dmt-D-Arg-Phe-Orn-NH 2 ,

3′5′Dmt-D-Arg-Phe-Dab-NH 2 ,

3′5′Dmt-D-Arg-Phe-Dap-NH 2 ,

Tyr-D-Arg-Tyr-Lys-NH 2 ,

Tyr-D-Arg-Tyr-Orn-NH 2 ,

Tyr-D-Arg-Tyr-Dab-NH 2 ,

Tyr-D-Arg-Tyr-Dap-NH 2 ,

2′6′Dmt-D-Arg-Tyr-Lys-NH 2 ,

2′6′Dmt-D-Arg-Tyr-Orn-NH 2 ,

2′6′Dmt-D-Arg-Tyr-Dab-NH 2 ,

2′6′Dmt-D-Arg-Tyr-Dap-NH 2 ,

2′6′Dmt-D-Arg-2′6′Dmt-Lys-NH 2 ,

2′6′Dmt-D-Arg-2′6′Dmt-Orn-NH 2 ,

2′6′Dmt-D-Arg-2′6′Dmt-Dab-NH 2 ,

2′6′Dmt-D-Arg-2′6′Dmt-Dap-NH 2 ,

3′5Dmt-D-Arg-3′5Dmt-Arg-NH 2 ,

3′5Dmt-D-Arg-3′5Dmt-Lys-NH 2 ,

3′5Dmt-D-Arg-3′5Dmt-Orn-NH 2 ,

3′5Dmt-D-Arg-3′5Dmt-Dab-NH 2 ,

Tyr-D-Lys-Phe-Dap-NH 2 ,

Tyr-D-Lys-Phe-Arg-NH 2 ,

Tyr-D-Lys-Phe-Lys-NH 2 ,

Tyr-D-Lys-Phe-Orn-NH 2 ,

2′6′Dmt-D-Lys-Phe-Dab-NH 2

2′6′Dmt-D-Lys-Phe-Dap-NH 2 ,

2′6′Dmt-D-Lys-Phe-Arg-NH 2 ,

2′6′Dmt-D-Lys-Phe-Lys-NH 2 ,

3′5′Dmt-D-Lys-Phe-Orn-NH 2 ,

3′5′Dmt-D-Lys-Phe-Dab-NH 2 ,

3′5′Dmt-D-Lys-Phe-Dap-NH 2 ,

3′5′Dmt-D-Lys-Phe-Arg-NH 2 ,

Tyr-D-Lys-Tyr-Lys-NH 2 ,

Tyr-D-Lys-Tyr-Orn-NH 2 ,

Tyr-D-Lys-Tyr-Dab-NH 2 ,

Tyr-D-Lys-Tyr-Dap-NH 2 ,

2′6′Dmt-D-Lys-Tyr-Lys-NH 2 ,

2′6′Dmt-D-Lys-Tyr-Orn-NH 2 ,

2′6′Dmt-D-Lys-Tyr-Dab-NH 2 ,

2′6′Dmt-D-Lys-Tyr-Dap-NH 2 ,

2′6′Dmt-D-Lys-2′6′Dmt-Lys-NH 2 ,

2′6′Dmt-D-Lys-2′6′Dmt-Orn-NH 2 ,

2′6′Dmt-D-Lys-2′6′Dmt-Dab-NH 2 ,

2′6′Dmt-D-Lys-2′6′Dmt-Dap-NH 2 ,

2′6′Dmt-D-Arg-Phe-dnsDap-NH 2 ,

2′6′Dmt-D-Arg-Phe-atnDap-NH 2 ,

3′5′Dmt-D-Lys-3′5′Dmt-Lys-NH 2 ,

3′5′Dmt-D-Lys-3′5′Dmt-Orn-NH 2 ,

3′5′Dmt-D-Lys-3′5′Dmt-Dab-NH 2 ,

3′5′Dmt-D-Lys-3′5′Dmt-Dap-NH 2 ,

Tyr-D-Lys-Phe-Arg-NH 2 ,

Tyr-D-Orn-Phe-Arg-NH 2 ,

Tyr-D-Dab-Phe-Arg-NH 2 ,

Tyr-D-Dap-Phe-Arg-NH 2 ,

2′6′Dmt-D-Arg-Phe-Arg-NH 2 ,

2′6′Dmt-D-Lys-Phe-Arg-NH 2 ,

2′6′Dmt-D-Orn-Phe-Arg-NH 2 ,

2′6′Dmt-D-Dab-Phe-Arg-NH 2 ,

3′5′Dmt-D-Dap-Phe-Arg-NH 2 ,

3′5′Dmt-D-Arg-Phe-Arg-NH 2 ,

3′5′Dmt-D-Lys-Phe-Arg-NH 2 ,

3′5′Dmt-D-Orn-Phe-Arg-NH 2 ,

Tyr-D-Lys-Tyr-Arg-NH 2 ,

Tyr-D-Orn-Tyr-Arg-NH 2 ,

Tyr-D-Dab-Tyr-Arg-NH 2 ,

Tyr-D-Dap-Tyr-Arg-NH 2 ,

2′6′Dmt-D-Arg-2′6′Dmt-Arg-NH 2 ,

2′6′Dmt-D-Lys-2′6′Dmt-Arg-NH 2 ,

2′6′Dmt-D-Orn-2′6′Dmt-Arg-NH 2 ,

2′6′Dmt-D-Dab-2′6′Dmt-Arg-NH 2 ,

3′5′Dmt-D-Dap-3′5′Dmt-Arg-NH 2 ,

3′5′Dmt-D-Arg-3′5′Dmt-Arg-NH 2 ,

3′5′Dmt-D-Lys-3′5′Dmt-Arg-NH 2 ,

3′5′Dmt-D-Orn-3′5′Dmt-Arg-NH 2 ,

Mmt-D-Arg-Phe-Lys-NH 2 ,

Mmt-D-Arg-Phe-Orn-NH 2 ,

Mmt-D-Arg-Phe-Dab-NH 2 ,

Mmt-D-Arg-Phe-Dap-NH 2 ,

Tmt-D-Arg-Phe-Lys-NH 2 ,

Tmt-D-Arg-Phe-Orn-NH 2 ,

Tmt-D-Arg-Phe-Dab-NH 2 ,

Tmt-D-Arg-Phe-Dap-NH 2 ,

Hmt-D-Arg-Phe-Lys-NH 2 ,

Hmt-D-Arg-Phe-Orn-NH 2 ,

Hmt-D-Arg-Phe-Dab-NH 2 ,

Hmt-D-Arg-Phe-Dap-NH 2 ,

Mmt-D-Lys-Phe-Lys-NH 2 ,

Mmt-D-Lys-Phe-Orn-NH 2 ,

Mmt-D-Lys-Phe-Dab-NH 2 ,

Mmt-D-Lys-Phe-Dap-NH 2 ,

Mmt-D-Lys-Phe-Arg-NH 2 ,

Tmt-D-Lys-Phe-Lys-NH 2 ,

Tmt-D-Lys-Phe-Orn-NH 2 ,

Tmt-D-Lys-Phe-Dab-NH 2 ,

Tmt-D-Lys-Phe-Dap-NH 2 ,

Tmt-D-Lys-Phe-Arg-NH 2 ,

Hmt-D-Lys-Phe-Lys-NH 2 ,

Hmt-D-Lys-Phe-Orn-NH 2 ,

Hmt-D-Lys-Phe-Dab-NH 2 ,

Hmt-D-Lys-Phe-Dap-NH 2 ,

Hmt-D-Lys-Phe-Arg-NH 2 ,

Mmt-D-Lys-Phe-Arg-NH 2 ,

Mmt-D-Orn-Phe-Arg-NH 2 ,

Mmt-D-Dab-Phe-Arg-NH 2 ,

Mmt-D-Dap-Phe-Arg-NH 2 ,

Mmt-D-Arg-Phe-Arg-NH 2 ,

Tmt-D-Lys-Phe-Arg-NH 2 ,

Tmt-D-Orn-Phe-Arg-NH 2 ,

Tmt-D-Dab-Phe-Arg-NH 2 ,

Tmt-D-Dap-Phe-Arg-NH 2 ,

Tmt-D-Arg-Phe-Arg-NH 2 ,

Hmt-D-Lys-Phe-Arg-NH 2

Hmt-D-Orn-Phe-Arg-NH 2 ,

Hmt-D-Dab-Phe-Arg-NH 2 ,

Hmt-D-Dap-Phe-Arg-NH 2 ,

Hmt-D-Arg-Phe-Arg-NH 2 ,

D-Arg-2′6′Dmt-Lys-Phe-NH 2 ,

D-Arg-2′6′Dmt-Phe-Lys-NH 2 ,

D-Arg-Phe-Lys-2′6′Dmt-NH 2 ,

D-Arg-Phe-2′6′Dmt-Lys-NH 2 ,

D-Arg-Lys-2′6′Dmt-Phe-NH 2 ,

D-Arg-Lys-Phe-2′6′Dmt-NH 2 ,

Phe-Lys-2′6′Dmt-D-Arg-NH 2 ,

Phe-Lys-D-Arg-2′6′Dmt-NH 2 ,

Phe-D-Arg-2′6′Dmt-Lys-NH 2 ,

Phe-D-Arg-Lys-2′6′Dmt-NH 2 ,

Phe-2′6′Dmt-D-Arg-Lys-NH 2 ,

Phe-2′6′Dmt-Lys-D-Arg-NH 2 ,

Lys-Phe-D-Arg-2′6′Dmt-NH 2 ,

Lys-Phe-2′6′Dmt-D-Arg-NH 2 ,

Lys-2′6′Dmt-D-Arg-Phe-NH 2 ,

Lys-2′6′Dmt-Phe-D-Arg-NH 2 ,

Lys-D-Arg-Phe-2′6′Dmt-NH 2 ,

Lys-D-Arg-2′6′Dmt-Phe-NH 2 ,

D-Arg-2′6′Dmt-D-Arg-Phe-NH 2 ,

D-Arg-2′6′Dmt-D-Arg-2′6′Dmt-NH 2 ,

D-Arg-2′6′Dmt-D-Arg-Tyr-NH 2 ,

D-Arg-2′6′Dmt-D-Arg-Trp-NH 2 ,

Trp-D-Arg-Phe-Lys-NH 2 ,

Trp-D-Arg-Tyr-Lys-NH 2 ,

Trp-D-Arg-Trp-Lys-NH 2 ,

Trp-D-Arg-2′6′Dmt-Lys-NH 2

D-Arg-Trp-Lys-Phe-NH 2 ,

D-Arg-Trp-Phe-Lys-NH 2 ,

D-Arg-Trp-Lys-2′6′Dmt-NH 2

D-Arg-Trp-2′6′Dmt-Lys-NH 2 ,

D-Arg-Lys-Trp-Phe-NH 2 ,

D-Arg-Lys-Trp-2′6′Dmt-NH 2 ,

Cha-D-Arg-Phe-Lys-NH 2 ,

Ala-D-Arg-Phe-Lys-NH 2 .

16. The method of claim 15 , wherein the mammal is a human.

17. The method of claim 15 , wherein the peptide is administered orally, topically, intranasally, systemically, intravenously, subcutaneously, intramuscularly, intrathecally, or transdermally.

18. The method of claim 15 , wherein the peptide is combined with a pharmaceutically acceptable carrier prior to administration to the mammal.

19. The method of claim 15 , wherein the peptide has the amino acid sequence D-Arg-2′6′Dmt-Lys-Phe-NH 2 .

20. The method of claim 15 , wherein the peptide has the amino acid sequence 2′6′Dmt-D-Arg-Phe-Lys-NH 2 .

21. The method of claim 15 , wherein the peptide has the amino acid sequence Phe-D-Arg-Phe-Lys-NH 2 .

Assignments (5)

CONFIRMATORY LICENSE Recorded May 16, 2013

From: CORNELL UNIVERSITY / CORNELL RESEARCH FOUNDATION, INC.

To: NATIONAL INSTITUTES OF HEALTH (NIH), U.S. DEPT. OF HEALTH AND HUMAN SERVICES (DHHS), U.S. GOVERNMENT

Reel/Frame 030435/0507 →

AFFIDAVIT RE ERRONEOUS RECORDATION Recorded Jan 21, 2013

From: CORNELL RESEARCH FOUNDATION, INC. & INSTITUT DE RECHERCHES CLINIQUES DE MONTREAL

To: CORNELL RESEARCH FOUNDATION, INC; INSTITUT DE RECHERCHES CLINIQUES DE MONTREAL

Reel/Frame 029663/0979 →

ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jul 13, 2012

From: SILBERMANN, BRYAN T.; HUBER, THOMAS J.

To: LUMENIR, INC.

Reel/Frame 028545/0356 →

ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 14, 2012

From: SZETO, HAZEL H.; ZHAO, KESHENG

To: CORNELL RESEARCH FOUNDATION, INC.

Reel/Frame 027862/0344 →

ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 14, 2012

From: SCHILLER, PETER W.

To: INSTITUT DE RECHERCHES CLINIQUES DE MONTREAL

Reel/Frame 027863/0073 →

Continuity (6)

Continuation 12753403 · Apr 2, 2010

Continuation 11427804 · Jun 30, 2006

Continuation In Part 10771232 · Feb 3, 2004

Provisional Application 60444777 · Feb 4, 2003

Provisional Application 60535690 · Jan 8, 2004

Related Publication 20120021970A1 · Jan 26, 2012