Claims for Patent: 7,576,061

Summary for Patent: 7,576,061

Title:	Methods for preventing mitochondrial permeability transition
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 (pm) and the total number of amino acid residues (r) wherein 3pm 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 (pt) wherein 2a is the largest number that is less than or equal to pt+1, except that when a is 1, pt may also be 1.
Inventor(s):	Hazel H. Szeto, Kesheng Zhao, Peter W. Schiller
Assignee:	Institut de Recherches Cliniques de Montreal IRCM , Cornell Research Foundation Inc
Application Number:	US10/771,232
Patent Claims:	1. A method of reducing the number of mitochondria undergoing mitochondrial permeability transitioning (MPT), or preventing mitochondrial permeability transitioning in a mammal in need thereof, the method comprising administering to the mammal an effective amount of a peptide having the formula D-Arg-Dmt-Lys-Phe-NH2, D-Arg-Dmt-Phe-Lys-NH2, D-Arg-Phe-Lys-Dmt-NH2, D-Arg-Phe-Dmt-Lys-NH2, D-Arg-Lys-Dmt-Phe-NH2, D-Arg-Lys-Phe-Dmt-NH2, Phe-Lys-Dmt-D-Arg-NH2, Phe-Lys-D-Arg-Dmt-NH2, Phe-D-Arg-Dmt-Lys-NH2, Phe-D-Arg-Lys-Dmt-NH2, Phe-Dmt-D-Arg-Lys-NH2, Phe-Dmt-Lys-D-Arg-NH2, Lys-Phe-Dmt-D-Arg-NH2, Lys-Dmt-D-Arg-Phe-NH2, Lys-Dmt-Phe-D-Arg-NH2, Lys-D-Arg-Phe-Dmt-NH2, Lys-D-Arg-Dmt-Phe-NH2, D-Arg-Dmt-D-Arg-Phe-NH2, D-Arg-Dmt-D-Arg-Dmt-NH2, D-Arg-Dmt-D-Arg-Tyr-NH2, D-Arg-Dmt-D-Arg-Trp-NH2, Trp-D-Arg-Phe-Lys-NH2, Trp-D-Arg-Tyr-Lys-NH2, Trp-D-Arg-Trp-Lys-NH2, Trp-D-Arg-Dmt-Lys-NH2, D-Arg-Trp-Lys-Phe-NH2, D-Arg-Trp-Phe-Lys-NH2, D-Arg-Trp-Lys-Dmt-NH2, D-Arg-Trp-Dmt-Lys-NH2, D-Arg-Lys-Trp-Phe-NH2, D-Arg-Lys-Trp-Dmt-NH2, Cyclohexyl-D-Arg-Phe-Lys-NH2, or Ala-D-Arg-Phe-Lys-NH2. 2. A method according to claim 1, wherein the peptide has the formula D-Arg-Dmt-Lys-Phe-NH2. 3. The method according to claim 1, wherein the peptide is administered orally. 4. The method according to claim 1, wherein the peptide is administered topically. 5. The method according to claim 1, wherein the peptide is administered intranasally. 6. The method according to claim 1, wherein the peptide is administered systemically. 7. The method according to claim 6, wherein the peptide is administered intravenously. 8. The method according to claim 1, wherein the peptide is administered subcutaneously. 9. The method according to claim 1, wherein the peptide is administered intramuscularly. 10. The method according to claim 1, wherein the peptide is administered intracerebroventricularly. 11. The method according to claim 1, wherein the peptide is administered intrathecally. 12. The method according to claim 1, wherein the peptide is administered transdermally. 13. The method according to claim 12, wherein the transdermal administration is by iontophoresis. 14. The method according to claim 1, wherein the mammal is suffering from ischemia. 15. The method according to claim 1, wherein the mammal is suffering from reperfusion. 16. The method according to claim 1, wherein the mammal is suffering from hypoxia. 17. The method according to claim 14, wherein the ischemia is due to stroke. 18. The method according to claim 14, wherein the ischemia is intestinal ischemia. 19. The method according to claim 14, wherein the ischemia is present in a muscle tissue. 20. The method according to claim 19, wherein the muscle tissue is cardiac muscle tissue. 21. The method according to claim 19, wherein the muscle tissue is skeletal muscle tissue. 22. The method according to claim 19, wherein the muscle tissue is smooth muscle tissue. 23. The method according to claim 1, wherein the mammal is suffering from hypoxia. 24. The method according to claim 1, wherein the mammal is suffering from drug-induced MPT. 25. The method according to claim 1, wherein the mammal is a human. 26. A method of reducing the number of mitochondria undergoing mitochondrial permeability transitioning (MPT), or preventing mitochondrial permeability transitioning in a mammal in need thereof, the method comprising administering to the mammal an effective amount of a peptide having the formula D-Arg-Dmt-Lys-Phe-NH2, D-Arg-Dmt-Phe-Lys-NH2, D-Arg-Phe-Lys-Dmt-NH2, D-Arg-Phe-Dmt-Lys-NH2, D-Arg-Lys-Dmt-Phe-NH2, D-Arg-Lys-Phe-Dmt-NH2, Phe-Lys-Dmt-D-Arg-NH2, Phe-Lys-D-Arg-Dmt-NH2, Phe-D-Arg-Dmt-Lys-NH2, Phe-D-Arg-Lys-Dmt-NH2, Phe-Dmt-D-Arg-Lys-NH2, Phe-Dmt-Lys-D-Arg-NH2, Lys-Phe-Dmt-D-Arg-NH2, Lys-Dmt-D-Arg-Phe-NH2, Lys-Dmt-Phe-D-Arg-NH2, Lys-D-Arg-Phe-Dmt-NH2, Lys-D-Arg-Dmt-Phe-NH2, D-Arg-Dmt-D-Arg-Phe-NH2, D-Arg-Dmt-D-Arg-Dmt-NH2, D-Arg-Dmt-D-Arg-Tyr-NH2, D-Arg-Dmt-D-Arg-Trp-NH2, Trp-D-Arg-Phe-Lys-NH2, Trp-D-Arg-Tyr-Lys-NH2, Trp-D-Arg-Trp-Lys-NH2, Trp-D-Arg-Dmt-Lys-NH2, D-Arg-Trp-Lys-Phe-NH2, D-Arg-Trp-Phe-Lys-NH2, D-Arg-Trp-Lys-Dmt-NH2, D-Arg-Trp-Dmt-Lys-NH2, D-Arg-Lys-Trp-Phe-NH2, D-Arg-Lys-Trp-Dmt-NH2, Cyclohexyl-D-Arg-Phe-Lys-NH2, or Ala-D-Arg-Phe-Lys-NH2, wherein the peptide is administered to the mammal as a composition comprising a pharmaceutically acceptable carrier. 27. The method according to claim 26, wherein the compound has the formula D-Arg-Dmt-Lys-Phe-NH2. 28. A method of reducing the number of mitochondria undergoing mitochondrial permeability transitioning (MPT), or preventing mitochondrial permeability transitioning in a mammal in need thereof, the method comprising administering to the mammal an effective amount of a peptide having the formula Phe-D-Arg-Phe-Lys-NH2 or Dmp-D-Arg-Phe-Lys-NH2. 29. A method of reducing the number of mitochondria undergoing mitochondrial permeability transitioning (MPT), or preventing mitochondrial permeability transitioning in a mammal in need thereof, the method comprising administering to the mammal an effective amount of a peptide having the formula Phe-D-Arg-Phe-Lys-NH2 or Dmp-D-Arg-Phe-Lys-NH2, wherein the peptide is administered to the mammal as a composition comprising a pharmaceutically acceptable carrier. 30. A method of reducing the number of mitochondria undergoing mitochondrial permeability transitioning (MPT), or preventing mitochondrial permeability transitioning in a mammal in need thereof, the method comprising administering to the mammal an effective amount of a peptide having the formula Lys-D-Arg-Tyr-NH2, Phe-D-Arg-His, D-Tyr-Trp-Lys-NH2, Trp-D-Lys-Tyr-Arg-NH2, Tyr-His-D-Gly-Met, Phe-Arg-D-His-Asp, Tyr-D-Arg-Phe-Lys-Glu-NH2 (SEQ. ID. NO: 3), Met-Tyr-D-Lys-Phe-Arg (SEQ. ID. NO: 4), D-His-Glu-Lys-Tyr-D-Phe-Arg (SEQ. ID. NO: 5), Lys-D-Gln-Tyr-Arg-D-Phe-Trp-NH2 (SEQ. ID. NO: 6), Phe-D-Arg-Lys-Trp-Tyr-D-Arg-His (SEQ. ID. NO: 7), Gly-D-Phe-Lys-Tyr-His-D-Arg-Tyr-NH2 (SEQ. ID. NO: 8), Val-D-Lys-His-Tyr-D-Phe-Ser-Tyr-Arg-NH2 (SEQ. ID. NO: 9), Trp-Lys-Phe-D-Asp-Arg-Tyr-D-His-Lys (SEQ. ID. NO: 10), Lys-Trp-D-Tyr-Arg-Asn-Phe-Tyr-D-His-NH2 (SEQ. ID. NO: 11), Thr-Gly-Tyr-Arg-D-His-Phe-Trp-D-His-Lys (SEQ. ID. NO: 12), Asp-D-Trp-Lys-Tyr-D-His-Phe-Arg-D-Gly-Lys-NH2 (SEQ. ID. NO: 13), D-His-Lys-Tyr-D-Phe-Glu-D-Asp-D-His-D-Lys-Arg-Trp-NH2 (SEQ. ID. NO: 14), Ala-D-Phe-D-Arg-Tyr-Lys-D-Trp-His-D-Tyr-Gly-Phe (SEQ. ID. NO: 15), Tyr-D-His-Phe-D-Arg-Asp-Lys-D-Arg-His-Trp-D-His-Phe (SEQ. ID. NO: 16), Phe-Phe-D-Tyr-Arg-Glu-Asp-D-Lys-Arg-D-Arg-His-Phe-NH2 (SEQ. ID. NO: 17), Phe-Tyr-Lys-D-Arg-Trp-His-D-Lys-D-Lys-Glu-Arg-D-Tyr-Thr (SEQ. ID. NO: 18), Tyr-Asp-D-Lys-Tyr-Phe-D-Lys-D-Arg-Phe-Pro-D-Tyr-His-Lys (SEQ. ID. NO: 19), Glu-Arg-D-Lys-Tyr-D-Val-Phe-D-His-Trp-Arg-D-Gly-Tyr-Arg-D-Met-NH2 (SEQ. ID. NO: 20), Arg-D-Leu-D-Tyr-Phe-Lys-Glu-D-Lys-Arg-D-Trp-Lys-D-Phe-Tyr-D-Arg-Gly (SEQ. ID. NO: 21), D-Glu-Asp-Lys-D-Arg-D-His-Phe-Phe-D-Val-Tyr-Arg-Tyr-D-Tyr-Arg-His-Phe-NH2 (SEQ. ID. NO: 22), Asp-Arg-D-Phe-Cys-Phe-D-Arg-D-Lys-Tyr-Arg-D-Tyr-Trp-D-His-Tyr-D-Phe-Lys-Phe (SEQ. ID. NO: 23), His-Tyr-D-Arg-Trp-Lys-Phe-D-Asp-Ala-Arg-Cys-D-Tyr-His-Phe-D-Lys-Tyr-His-Ser-NH2 (SEQ. ID. NO: 24), Gly-Ala-Lys-Phe-D-Lys-Glu-Arg-Tyr-His-D-Arg-D-Arg-Asp-Tyr-Trp-D-His-Trp-His-D-Lys-Asp (SEQ. ID. NO: 25), or 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-NH2 (SEQ. ID. NO: 26). 31. A method of reducing the number of mitochondria undergoing mitochondrial permeability transitioning (MPT), or preventing mitochondrial permeability transitioning in a mammal in need thereof, the method comprising administering to the mammal an effective amount of a peptide having the formula Lys-D-Arg-Tyr-NH2, Phe-D-Arg-His, D-Tyr-Trp-Lys-NH2, Trp-D-Lys-Tyr-Arg-NH2, Tyr-His-D-Gly-Met, Phe-Arg-D-His-Asp, Tyr-D-Arg-Phe-Lys-Glu-NH2 (SEQ. ID. NO: 3), Met-Tyr-D-Lys-Phe-Arg (SEQ. ID. NO: 4), D-His-Glu-Lys-Tyr-D-Phe-Arg (SEQ. ID. NO: 5), Lys-D-Gln-Tyr-Arg-D-Phe-Trp-NH2 (SEQ. ID. NO: 6), Phe-D-Arg-Lys-Trp-Tyr-D-Arg-His (SEQ. ID. NO: 7), Gly-D-Phe-Lys-Tyr-His-D-Arg-Tyr-NH2 (SEQ. ID. NO: 8), Val-D-Lys-His-Tyr-D-Phe-Ser-Tyr-Arg-NH2 (SEQ. ID. NO: 9), Trp-Lys-Phe-D-Asp-Arg-Tyr-D-His-Lys (SEQ. ID. NO: 10), Lys-Trp-D-Tyr-Arg-Asn-Phe-Tyr-D-His-NH2 (SEQ. ID. NO: 11), Thr-Gly-Tyr-Arg-D-His-Phe-Trp-D-His-Lys (SEQ. ID. NO: 12), Asp-D-Trp-Lys-Tyr-D-His-Phe-Arg-D-Gly-Lys-NH2 (SEQ. ID. NO: 13), D-His-Lys-Tyr-D-Phe-Glu-D-Asp-D-His-D-Lys-Arg-Trp-NH2 (SEQ. ID. NO: 14), Ala-D-Phe-D-Arg-Tyr-Lys-D-Trp-His-D-Tyr-Gly-Phe (SEQ. ID. NO: 15), Tyr-D-His-Phe-D-Arg-Asp-Lys-D-Arg-His-Trp-D-His-Phe (SEQ. ID. NO: 16), Phe-Phe-D-Tyr-Arg-Glu-Asp-D-Lys-Arg-D-Arg-His-Phe-NH2 (SEQ. ID. NO: 17), Phe-Tyr-Lys-D-Arg-Trp-His-D-Lys-D-Lys-Glu-Arg-D-Tyr-Thr (SEQ. ID. NO: 18), Tyr-Asp-D-Lys-Tyr-Phe-D-Lys-D-Arg-Phe-Pro-D-Tyr-His-Lys (SEQ. ID. NO: 19), Glu-Arg-D-Lys-Tyr-D-Val-Phe-D-His-Trp-Arg-D-Gly-Tyr-Arg-D-Met-NH2 (SEQ. ID. NO: 20), Arg-D-Leu-D-Tyr-Phe-Lys-Glu-D-Lys-Arg-D-Trp-Lys-D-Phe-Tyr-D-Arg-Gly (SEQ. ID. NO: 21), D-Glu-Asp-Lys-D-Arg-D-His-Phe-Phe-D-Val-Tyr-Arg-Tyr-D-Tyr-Arg-His-Phe-NH2 (SEQ. ID. NO: 22), Asp-Arg-D-Phe-Cys-Phe-D-Arg-D-Lys-Tyr-Arg-D-Tyr-Trp-D-His-Tyr-D-Phe-Lys-Phe (SEQ. ID. NO: 23), His-Tyr-D-Arg-Trp-Lys-Phe-D-Asp-Ala-Arg-Cys-D-Tyr-His-Phe-D-Lys-Tyr-His-Ser-NH2 (SEQ. ID. NO: 24), Gly-Ala-Lys-Phe-D-Lys-Glu-Arg-Tyr-His-D-Arg-D-Arg-Asp-Tyr-Trp-D-His-Trp-His-D-Lys-Asp (SEQ. ID. NO: 25), or 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-NH2 (SEQ. ID. NO: 26), wherein the peptide is administered to the mammal as a composition comprising a pharmaceutically acceptable carrier. 32. A method of reducing the number of mitochondria undergoing mitochondrial permeability transitioning (MPT), or preventing mitochondrial permeability transitioning in a removed organ of a mammal, the method comprising administering to the removed organ an effective amount of a peptide having the formula D-Arg-Dmt-Lys-Phe-NH2, D-Arg-Dmt-Phe-Lys-NH2, D-Arg-Phe-Lys-Dmt-NH2, D-Arg-Phe-Dmt-Lys-NH2, D-Arg-Lys-Dmt-Phe-NH2, D-Arg-Lys-Phe-Dmt-NH2, Phe-Lys-Dmt-D-Arg-NH2, Phe-Lys-D-Arg-Dmt-NH2, Phe-D-Arg-Dmt-Lys-NH2, Phe-D-Arg-Lys-Dmt-NH2, Phe-Dmt-D-Arg-Lys-NH2, Phe-Dmt-Lys-D-Arg-NH2, Lys-Phe-Dmt-D-Arg-NH2, Lys-Dmt-D-Arg-Phe-NH2, Lys-Dmt-Phe-D-Arg-NH2, Lys-D-Arg-Phe-Dmt-NH2, Lys-D-Arg-Dmt-Phe-NH2, D-Arg-Dmt-D-Arg-Phe-NH2, D-Arg-Dmt-D-Arg-Dmt-NH2, D-Arg-Dmt-D-Arg-Tyr-NH2, D-Arg-Dmt-D-Arg-Trp-NH2, Trp-D-Arg-Phe-Lys-NH2, Trp-D-Arg-Tyr-Lys-NH2, Trp-D-Arg-Trp-Lys-NH2, Trp-D-Arg-Dmt-Lys-NH2, D-Arg-Trp-Lys-Phe-NH2, D-Arg-Trp-Phe-Lys-NH2, D-Arg-Trp-Lys-Dmt-NH2, D-Arg-Trp-Dmt-Lys-NH2, D-Arg-Lys-Trp-Phe-NH2, D-Arg-Lys-Trp-Dmt-NH2, Cyclohexyl-D-Arg-Phe-Lys-NH2, or Ala-D-Arg-Phe-Lys-NH2. 33. The method according to claim 32, wherein the peptide has the formula D-Arg-Dmt-Lys-Phe-NH2. 34. A method of reducing the number of mitochondria undergoing mitochondrial permeability transitioning (MPT), or preventing mitochondrial permeability transitioning in a removed organ of a mammal, the method comprising administering to the removed organ an effective amount of a peptide having the formula D-Arg-Dmt-Lys-Phe-NH2, D-Arg-Dmt-Phe-Lys-NH2, D-Arg-Phe-Lys-Dmt-NH2, D-Arg-Phe-Dmt-Lys-NH2, D-Arg-Lys-Dmt-Phe-NH2, D-Arg-Lys-Phe-Dmt-NH2, Phe-Lys-Dmt-D-Arg-NH2, Phe-Lys-D-Arg-Dmt-NH2, Phe-D-Arg-Dmt-Lys-NH2, Phe-D-Arg-Lys-Dmt-NH2, Phe-Dmt-D-Arg-Lys-NH2, Phe-Dmt-Lys-D-Arg-NH2, Lys-Phe-Dmt-D-Arg-NH2, Lys-Dmt-D-Arg-Phe-NH2, Lys-Dmt-Phe-D-Arg-NH2, Lys-D-Arg-Phe-Dmt-NH2, Lys-D-Arg-Dmt-Phe-NH2, D-Arg-Dmt-D-Arg-Phe-NH2, D-Arg-Dmt-D-Arg-Dmt-NH2, D-Arg-Dmt-D-Arg-Tyr-NH2, D-Arg-Dmt-D-Arg-Trp-NH2, Trp-D-Arg-Phe-Lys-NH2, Trp-D-Arg-Tyr-Lys-NH2, Trp-D-Arg-Trp-Lys-NH2, Trp-D-Arg-Dmt-Lys-NH2, D-Arg-Trp-Lys-Phe-NH2, D-Arg-Trp-Phe-Lys-NH2, D-Arg-Trp-Lys-Dmt-NH2, D-Arg-Trp-Dmt-Lys-NH2, D-Arg-Lys-Trp-Phe-NH2, D-Arg-Lys-Trp-Dmt-NH2, Cyclohexyl-D-Arg-Phe-Lys-NH2, or Ala-D-Arg-Phe-Lys-NH2, wherein the peptide is administered to the removed organ as a composition comprising a pharmaceutically acceptable carrier. 35. The method according to claim 34, wherein the peptide has the formula D-Arg-Dmt-Lys-Phe-NH2. 36. A method of reducing the number of mitochondria undergoing mitochondrial permeability transitioning (MPT), or preventing mitochondrial permeability transitioning in a removed organ of a mammal, the method comprising administering to the removed organ an effective amount of a peptide having the formula Phe-D-Arg-Phe-Lys-NH2 or Dmp-D-Arg-Phe-Lys-NH2. 37. A method of reducing the number of mitochondria undergoing mitochondrial permeability transitioning (MPT), or preventing mitochondrial permeability transitioning in a removed organ of a mammal, the method comprising administering to the removed organ an effective amount of a peptide having the formula Phe-D-Arg-Phe-Lys-NH2 or Dmp-D-Arg-Phe-Lys-NH2, wherein the peptide is administered to the removed organ as a composition comprising a pharmaceutically acceptable carrier. 38. A method of reducing the number of mitochondria undergoing mitochondrial permeability transitioning (MPT), or preventing mitochondrial permeability transitioning in a removed organ of a mammal, the method comprising administering to the removed organ an effective amount of a peptide having the formula Lys-D-Arg-Tyr-NH2, Phe-D-Arg-His, D-Tyr-Trp-Lys-NH2, Trp-D-Lys-Tyr-Arg-NH2, Tyr-His-D-Gly-Met, Phe-Arg-D-His-Asp, Tyr-D-Arg-Phe-Lys-Glu-NH2 (SEQ. ID. NO: 3), Met-Tyr-D-Lys-Phe-Arg (SEQ. ID. NO: 4), D-His-Glu-Lys-Tyr-D-Phe-Arg (SEQ. ID. NO: 5), Lys-D-Gln-Tyr-Arg-D-Phe-Trp-NH2 (SEQ. ID. NO: 6), Phe-D-Arg-Lys-Trp-Tyr-D-Arg-His (SEQ. ID. NO: 7), Gly-D-Phe-Lys-Tyr-His-D-Arg-Tyr-NH2 (SEQ. ID. NO: 8), Val-D-Lys-His-Tyr-D-Phe-Ser-Tyr-Arg-NH2 (SEQ. ID. NO: 9), Trp-Lys-Phe-D-Asp-Arg-Tyr-D-His-Lys (SEQ. ID. NO: 10), Lys-Trp-D-Tyr-Arg-Asn-Phe-Tyr-D-His-NH2 (SEQ. ID. NO: 11), Thr-Gly-Tyr-Arg-D-His-Phe-Trp-D-His-Lys (SEQ. ID. NO: 12), Asp-D-Trp-Lys-Tyr-D-His-Phe-Arg-D-Gly-Lys-NH2 (SEQ. ID. NO: 13), D-His-Lys-Tyr-D-Phe-Glu-D-Asp-D-His-D-Lys-Arg-Trp-NH2 (SEQ. ID. NO: 14), Ala-D-Phe-D-Arg-Tyr-Lys-D-Trp-His-D-Tyr-Gly-Phe (SEQ. ID. NO: 15), Tyr-D-His-Phe-D-Arg-Asp-Lys-D-Arg-His-Trp-D-His-Phe (SEQ. ID. NO: 16), Phe-Phe-D-Tyr-Arg-Glu-Asp-D-Lys-Arg-D-Arg-His-Phe-NH2 (SEQ. ID. NO: 17), Phe-Tyr-Lys-D-Arg-Trp-His-D-Lys-D-Lys-Glu-Arg-D-Tyr-Thr (SEQ. ID. NO: 18), Tyr-Asp-D-Lys-Tyr-Phe-D-Lys-D-Arg-Phe-Pro-D-Tyr-His-Lys (SEQ. ID. NO: 19), Glu-Arg-D-Lys-Tyr-D-Val-Phe-D-His-Trp-Arg-D-Gly-Tyr-Arg-D-Met-NH2 (SEQ. ID. NO: 20), Arg-D-Leu-D-Tyr-Phe-Lys-Glu-D-Lys-Arg-D-Trp-Lys-D-Phe-Tyr-D-Arg-Gly (SEQ. ID. NO: 21), D-Glu-Asp-Lys-D-Arg-D-His-Phe-Phe-D-Val-Tyr-Arg-Tyr-D-Tyr-Arg-His-Phe-NH2 (SEQ. ID. NO: 22), Asp-Arg-D-Phe-Cys-Phe-D-Arg-D-Lys-Tyr-Arg-D-Tyr-Trp-D-His-Tyr-D-Phe-Lys-Phe (SEQ. ID. NO: 23), His-Tyr-D-Arg-Trp-Lys-Phe-D-Asp-Ala-Arg-Cys-D-Tyr-His-Phe-D-Lys-Tyr-His-Ser-NH2 (SEQ. ID. NO: 24), Gly-Ala-Lys-Phe-D-Lys-Glu-Arg-Tyr-His-D-Arg-D-Arg-Asp-Tyr-Trp-D-His-Trp-His-D-Lys-Asp (SEQ. ID. NO: 25), or 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-NH2 (SEQ. ID. NO: 26). 39. A method of reducing the number of mitochondria undergoing mitochondrial permeability transitioning (MPT), or preventing mitochondrial permeability transitioning in a removed organ of a mammal, the method comprising administering to the removed organ an effective amount of a peptide having the formula Lys-D-Arg-Tyr-NH2, Phe-D-Arg-His, D-Tyr-Trp-Lys-NH2, Trp-D-Lys-Tyr-Arg-NH2, Tyr-His-D-Gly-Met, Phe-Arg-D-His-Asp, Tyr-D-Arg-Phe-Lys-Glu-NH2 (SEQ. ID. NO: 3), Met-Tyr-D-Lys-Phe-Arg (SEQ. ID. NO: 4), D-His-Glu-Lys-Tyr-D-Phe-Arg (SEQ. ID. NO: 5), Lys-D-Gln-Tyr-Arg-D-Phe-Trp-NH2 (SEQ. ID. NO: 6), Phe-D-Arg-Lys-Trp-Tyr-D-Arg-His (SEQ. ID. NO: 7), Gly-D-Phe-Lys-Tyr-His-D-Arg-Tyr-NH2 (SEQ. ID. NO: 8), Val-D-Lys-His-Tyr-D-Phe-Ser-Tyr-Arg-NH2 (SEQ. ID. NO: 9), Trp-Lys-Phe-D-Asp-Arg-Tyr-D-His-Lys (SEQ. ID. NO: 10), Lys-Trp-D-Tyr-Arg-Asn-Phe-Tyr-D-His-NH2 (SEQ. ID. NO: 11), Thr-Gly-Tyr-Arg-D-His-Phe-Trp-D-His-Lys (SEQ. ID. NO: 12), Asp-D-Trp-Lys-Tyr-D-His-Phe-Arg-D-Gly-Lys-NH2 (SEQ. ID. NO: 13), D-His-Lys-Tyr-D-Phe-Glu-D-Asp-D-His-D-Lys-Arg-Trp-NH2 (SEQ. ID. NO: 14), Ala-D-Phe-D-Arg-Tyr-Lys-D-Trp-His-D-Tyr-Gly-Phe (SEQ. ID. NO: 15), Tyr-D-His-Phe-D-Arg-Asp-Lys-D-Arg-His-Trp-D-His-Phe (SEQ. ID. NO: 16), Phe-Phe-D-Tyr-Arg-Glu-Asp-D-Lys-Arg-D-Arg-His-Phe-NH2 (SEQ. ID. NO: 17), Phe-Tyr-Lys-D-Arg-Trp-His-D-Lys-D-Lys-Glu-Arg-D-Tyr-Thr (SEQ. ID. NO: 18), Tyr-Asp-D-Lys-Tyr-Phe-D-Lys-D-Arg-Phe-Pro-D-Tyr-His-Lys (SEQ. ID. NO: 19), Glu-Arg-D-Lys-Tyr-D-Val-Phe-D-His-Trp-Arg-D-Gly-Tyr-Arg-D-Met-NH2 (SEQ. ID. NO: 20), Arg-D-Leu-D-Tyr-Phe-Lys-Glu-D-Lys-Arg-D-Trp-Lys-D-Phe-Tyr-D-Arg-Gly (SEQ. ID. NO: 21), D-Glu-Asp-Lys-D-Arg-D-His-Phe-Phe-D-Val-Tyr-Arg-Tyr-D-Tyr-Arg-His-Phe-NH2 (SEQ. ID. NO: 22), Asp-Arg-D-Phe-Cys-Phe-D-Arg-D-Lys-Tyr-Arg-D-Tyr-Trp-D-His-Tyr-D-Phe-Lys-Phe (SEQ. ID. NO: 23), His-Tyr-D-Arg-Trp-Lys-Phe-D-Asp-Ala-Arg-Cys-D-Tyr-His-Phe-D-Lys-Tyr-His-Ser-NH2 (SEQ. ID. NO: 24), Gly-Ala-Lys-Phe-D-Lys-Glu-Arg-Tyr-His-D-Arg-D-Arg-Asp-Tyr-Trp-D-His-Trp-His-D-Lys-Asp (SEQ. ID. NO: 25), or 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-NH2 (SEQ. ID. NO: 26), wherein the peptide is administered to the removed organ as a composition comprising a pharmaceutically acceptable carrier. 40. A peptide having the formula D-Arg-Dmt-Lys-Phe-NH2, D-Arg-Dmt-Phe-Lys-NH2, D-Arg-Phe-Lys-Dmt-NH2, D-Arg-Phe-Dmt-Lys-NH2, D-Arg-Lys-Dmt-Phe-NH2, D-Arg-Lys-Phe-Dmt-NH2, Phe-Lys-Dmt-D-Arg-NH2, Phe-Lys-D-Arg-Dmt-NH2, Phe-D-Arg-Dmt-Lys-NH2, Phe-D-Arg-Lys-Dmt-NH2, Phe-Dmt-D-Arg-Lys-NH2, Phe-Dmt-Lys-D-Arg-NH2, Lys-Phe-Dmt-D-Arg-NH2, Lys-Dmt-D-Arg-Phe-NH2, Lys-Dmt-Phe-D-Arg-NH2, Lys-D-Arg-Phe-Dmt-NH2, Lys-D-Arg-Dmt-Phe-NH2, D-Arg-Dmt-D-Arg-Phe-NH2, D-Arg-Dmt-D-Arg-Dmt-NH2, D-Arg-Dmt-D-Arg-Tyr-NH2, D-Arg-Dmt-D-Arg-Trp-NH2, Trp-D-Arg-Phe-Lys-NH2, Trp-D-Arg-Tyr-Lys-NH2, Trp-D-Arg-Trp-Lys-NH2, Trp-D-Arg-Dmt-Lys-NH2, D-Arg-Trp-Lys-Phe-NH2, D-Arg-Trp-Phe-Lys-NH2, D-Arg-Trp-Lys-Dmt-NH2, D-Arg-Trp-Dmt-Lys-NH2, D-Arg-Lys-Trp-Phe-NH2, D-Arg-Lys-Trp-Dmt-NH2, Cyclohexyl-D-Arg-Phe-Lys-NH2, or Ala-D-Arg-Phe-Lys-NH2. 41. A peptide according to claim 40, wherein the peptide has the formula D-Arg-Dmt-Lys-Phe-NH2. 42. A composition comprising a peptide having the formula D-Arg-Dmt-Lys-Phe-NH2, D-Arg-Dmt-Phe-Lys-NH2, D-Arg-Phe-Lys-Dmt-NH2, D-Arg-Phe-Dmt-Lys-NH2, D-Arg-Lys-Dmt-Phe-NH2, D-Arg-Lys-Phe-Dmt-NH2, Phe-Lys-Dmt-D-Arg-NH2, Phe-Lys-D-Arg-Dmt-NH2, Phe-D-Arg-Dmt-Lys-NH2, Phe-D-Arg-Lys-Dmt-NH2, Phe-Dmt-D-Arg-Lys-NH2, Phe-Dmt-Lys-D-Arg-NH2, Lys-Phe-Dmt-D-Arg-NH2, Lys-Dmt-D-Arg-Phe-NH2, Lys-Dmt-Phe-D-Arg-NH2, Lys-D-Arg-Phe-Dmt-NH2, Lys-D-Arg-Dmt-Phe-NH2, D-Arg-Dmt-D-Arg-Phe-NH2, D-Arg-Dmt-D-Arg-Dmt-NH2, D-Arg-Dmt-D-Arg-Tyr-NH2, D-Arg-Dmt-D-Arg-Trp-NH2, Trp-D-Arg-Phe-Lys-NH2, Trp-D-Arg-Tyr-Lys-NH2, Trp-D-Arg-Trp-Lys-NH2, Trp-D-Arg-Dmt-Lys-NH2, D-Arg-Trp-Lys-Phe-NH2, D-Arg-Trp-Phe-Lys-NH2, D-Arg-Trp-Lys-Dmt-NH2, D-Arg-Trp-Dmt-Lys-NH2, D-Arg-Lys-Trp-Phe-NH2, D-Arg-Lys-Trp-Dmt-NH2, Cyclohexyl-D-Arg-Phe-Lys-NH2, or Ala-D-Arg-Phe-Lys-NH2, and a pharmaceutically acceptable carrier. 43. A composition according to claim 42, wherein the peptide has the formula D-Arg-Dmt-Lys-Phe-NH2. 44. A peptide having the formula Phe-D-Arg-Phe-Lys-NH2 or Dmp-D-Arg-Phe-Lys-NH2. 45. A composition comprising a peptide having the formula Phe-D-Arg-Phe-Lys-NH2 or Dmp-D-Arg-Phe-Lys-NH2 and a pharmaceutically acceptable carrier.