METHODS FOR PREVENTING OR TREATING MITOCHONDRIAL PERMEABILITY TRANSITION
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 3p 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.
1 . 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 an aromatic-cationic peptide having:
(a) at least one net positive charge;
(b) a minimum of four amino acids;
(c) a maximum of about twenty amino acids;
(d) a relationship between the minimum number of net positive charges (p m ) and the total number of amino acid residues (r) wherein 3p m is the largest number that is less than or equal to r+1; and
(e) a relationship between the minimum number of aromatic groups (a) and the total number of net positive charges (p t ) wherein 2a 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.
2 . The method according to claim 1 , wherein 2 p m is the largest number that is less than or equal to r+1.
3 . The method according to claim 1 , wherein a is equal to p t .
4 . The method according to claim 1 , wherein the peptide has a minimum of two positive charges.
5 . The method according to claim 1 , wherein the peptide has a minimum of three positive charges.
6 . The method according to claim 1 , wherein the peptide is water soluble.
7 . The method according to claim 1 , wherein the peptide comprises one or more D-amino acids.
8 . The method according to claim 1 , wherein the C-terminal carboxyl group of the amino acid at the C-terminus is amidated.
9 . The method according to claim 1 , wherein the peptide comprises one or more non-naturally occurring amino acids.
10 . The method according to claim 1 , wherein the peptide has a minimum of four amino acids.
11 . The method according to claim 1 , wherein the peptide has a maximum of about twelve amino acids.
12 . The method according to claim 1 , wherein the peptide has a maximum of about nine amino acids.
13 . The method according to claim 1 , wherein the peptide has a maximum of about six amino acids.
14 . The method according to claim 1 , wherein the peptide has mu-opioid receptor agonist activity.
15 . The method according to claim 1 , wherein the peptide does not have mu-opioid receptor agonist activity.
16 . The method according to claim 1 , wherein the mammal is a human.