Methods for preventing mitochondrial permeability transition
AssigneesCornell Research Foundation, Inc., Institute de Recherches Clinques de Montreal
InventorsHazel H. Szeto, Kesheng Zhao, Peter W. Schiller
Life of this patent
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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 (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.
Claims45
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.
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.
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.
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.
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).
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.
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.
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.
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.
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.
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).
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.
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.
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.
A peptide having the formula Phe-D-Arg-Phe-Lys-NH2 or Dmp-D-Arg-Phe-Lys-NH2.
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.
Dependencies are inferred from the claim text.