Claims
- 1. A peptide that ameliorates a symptom of atherosclerosis, wherein said peptide comprises an amino acid sequence that:
ranges in length from about 10 to about 30 amino acids; comprises at least one class A amphipathic helix; comprises at least one “D” amino acid residue; protects a phospholipid against oxidation by an oxidizing agent; and is not the D-18A peptide.
- 2. The peptide of claim 1, wherein said peptide further comprises a protecting group.
- 3. The peptide of claim 1, wherein said peptide further comprises a protecting group coupled to the amino or carboxyl terminus.
- 4. The peptide of claim 2, wherein said protecting group is a protecting group selected from the group consisting of acetyl, amide, 3 to 20 carbon alkyl groups, Fmoc, t-boc, 9-fluoreneacetyl group, 1-fluorenecarboxylic group, 9-florenecarboxylic group, 9-fluorenone-1-carboxylic group, benzyloxycarbonyl, Xanthyl (Xan), Trityl (Trt), 4-methyltrityl (Mtt), 4-methoxytrityl (Mmt), 4-methoxy-2,3,6-trimethyl-benzenesulphonyl (Mtr), Mesitylene-2-sulphonyl (Mts), 4,4=-dimethoxybenzhydryl (Mbh),Tosyl (Tos), 2,2,5,7,8-pentamethyl chroman-6-sulphonyl (Pmc), 4-methylbenzyl (MeBzl), 4-methoxybenzyl (MeOBzl), Benzyloxy (BzlO), Benzyl (Bzl), Benzoyl (Bz), 3-nitro-2-pyridinesulphenyl (Npys), 1-(4,4-dimentyl-2,6-diaxocyclohexylidene)ethyl (Dde), 2,6-dichlorobenzyl (2,6-DiCl-Bzl), 2-chlorobenzyloxycarbonyl (2-Cl-Z), 2-bromobenzyloxycarbonyl (2-Br-Z), Benzyloxymethyl (Bom), t-butoxycarbonyl (Boc), cyclohexyloxy (cHxO),t-butoxymethyl (Bum), t-butoxy (tBuO), t-Butyl (tBu), Acetyl (Ac), a benzoyl group, a carbobenzoxy group, a propyl group, a butyl group, a pentyl group, a hexyl group group, and Trifluoroacetyl (TFA).
- 5. The peptide of claim 1, wherein said peptide further comprises a first protecting group coupled to the amino terminus and a second protecting group coupled to the carboxyl terminus.
- 6. The peptide of claim 1, wherein all enantiomeric amino acids are “D” amino acids.
- 7. The peptide of claim 1, wherein said peptide has greater than about 50% amino acid sequence identity with human or mouse apo A-1.
- 8. The peptide of claim 1, wherein said peptide is mixed with a pharmacologically acceptable excipient.
- 9. The peptide of claim 1, wherein said peptide is mixed with a pharmacologically acceptable excipient suitable for oral administration to a mammal.
- 10. The peptide of claim 1, wherein said peptide comprises sequence selected from the group consisting of D-W-L-K-A-F-Y-D-K-V-A-E-K-L-K-E-A-F (SEQ ID NO: 2), D-W-F-K-A-F-Y-D-K-V-A-E-K-L-K-E-A-F (SEQ-ID-NO:3), D-W-L-K-A-F-Y-D-K-V-A-E-K-F-K-E-A-F (SEQ-ID-NO:4), D-W-F-K-A-F-Y-D-K-V-A-E-K-F-K-E-A-F(SEQ-ID-NO:5), D-W-L-K-A-F-Y-D-K-F-F-E-K-F-K-E-F-F (SEQ-ID-NO:6), D-W-F-K-A-F-Y-D-K-F-F-E-K-F-K-E-F-F (SEQ-ID-NO:7), D-W-L-K-A-F-Y-D-K-V-A-E-K-F-K-E-A-F (SEQ-ID-NO:8), D-W-L-K-A-F-Y-D-K-V-A-E-K-L-K-E-F-F (SEQ-ID-NO:9), D-W-L-K-A-F-Y-D-K-V-F-E-K-F-K-E-A-F (SEQ-ID-NO:10), D-W-L-K-A-F-Y-D-K-V-F-E-K-L-K-E-F-F (SEQ-ID-NO:11), D-W-L-K-A-F-Y-D-K-V-A-E-K-F-K-E-F-F (SEQ-ID-NO:12), D-W-L-K-A-F-Y-D-K-V-F-E-K-F-K-E-F-F (SEQ-ID-NO: 13), E-W-L-K-L-F-Y-E-K-V-L-E-K-F-K-E-A-F (SEQ-ID-NO:14), E-W-L-K-A-F-Y-D-K-V-A-E-K-F-K-E-A-F (SEQ-ID-NO:15), E-W-L-K-A-F-Y-D-K-V-A-E-K-L-K-E-F-F (SEQ-ID-NO:16), E-W-L-K-A-F-Y-D-K-V-F-E-K-F-K-E-A-F (SEQ-ID-NO:17), E-W-L-K-A-F-Y-D-K-V-F-E-K-L-K-E-F-F (SEQ-ID-NO:18), E-W-L-K-A-F-Y-D-K-V-A-E-K-F-K-E-F-F (SEQ-ID-NO:19), E-W-L-K-A-F-Y-D-K-V-F-E-K-F-K-E-F-F (SEQ ID NO: 20), A-F-Y-D-K-V-A-E-K-L-K-E-A-F (SEQ ID NO: 21), A-F-Y-D-K-V-A-E-K-F-K-E-A-F (SEQ ID NO:22), A-F-Y-D-K-V-A-E-K-F-K-E-A-F (SEQ ID NO:23), A-F-Y-D-K-F-F-E-K-F-K-E-F-F (SEQ ID NO:24), A-F-Y-D-K-F-F-E-K-F-K-E-F-F (SEQ ID NO:25), A-F-Y-D-K-V-A-E-K-F-K-E-A-F (SEQ ID NO:26), A-F-Y-D-K-V-A-E-K-L-K-E-F-F (SEQ ID NO:27), A-F-Y-D-K-V-F-E-K-F-K-E-A-F (SEQ ID NO:28), A-F-Y-D-K-V-F-E-K-L-K-E-F-F (SEQ ID NO:29), A-F-Y-D-K-V-A-E-K-F-K-E-F-F (SEQ ID NO:30), K-A-F-Y-D-K-V-F-E-K-F-K-E-F (SEQ ID NO:31), L-F-Y-E-K-V-L-E-K-F-K-E-A-F (SEQ ID NO:32), A-F-Y-D-K-V-A-E-K-F-K-E-A-F (SEQ ID NO:33), A-F-Y-D-K-V-A-E-K-L-K-E-F-F (SEQ ID NO:34), A-F-Y-D-K-V-F-E-K-F-K-E-A-F (SEQ ID NO:35), A-F-Y-D-K-V-F-E-K-L-K-E-F-F (SEQ ID NO:36), A-F-Y-D-K-V-A-E-K-F-K-E-F-F (SEQ ID NO:37), A-F-Y-D-K-V-F-E-K-F-K-E-F-F (SEQ ID NO:38).
- 11. The peptide of claim 10, wherein all enantiomeric amino acids are “D” amino acids.
- 12. The peptide of claim 10, wherein said peptide further comprises a protecting group coupled to the amino or carboxyl terminus.
- 13. The peptide of claim 12, wherein said peptide comprises a protecting group coupled to the amino terminal and said amino terminal protecting group is a protecting group selected from the group consisting of a benzoyl group, an acetyl, a propeonyl, a carbobenzoxy, a propyl, a butyl, a pentyl, a hexyl, and a 3 to 20 carbon alkyl.
- 14. The peptide of claim 12, wherein said peptide comprises a protecting group coupled to the carboxyl terminal and said carboxyl terminal protecting group is an amide.
- 15. The peptide of claim 10, wherein said peptide further comprises a first protecting group coupled to the amino terminus and a second protecting group coupled to the carboxyl terminus.
- 16. The peptide of claim 15, wherein said peptide further comprises:
a first protecting group coupled to the amino terminus wherein said protecting group is a protecting group selected from the group consisting of a benzoyl group, an acetyl, a propeonyl, a carbobenzoxy, a propyl, a butyl, a pentyl, a hexyl, and a 3 to 20 carbon alkyl; and a second protecting group coupled to the carboxyl terminal and said carboxyl terminal protecting group is an amide.
- 17. The peptide of claim 15, wherein all enantiomeric amino acids are “D” amino acids.
- 18. The peptide of claim 1, wherein said oxidizing agent is selected from the group consisting of hydrogen peroxide, 13(S)-HPODE, 15(S)-HPETE, HPODE, HPETE, HODE, and HETE.
- 19. The peptide of claim 1, wherein said phospholipid is selected from the group consisting of 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine (PAPC), 1-stearoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine (SAPC)), 1-stearoyl-2-arachidonyl-sn-glycero-3-phosphorylethanolamine (SAPE).
- 20. A composition suitable for oral administration that ameliorates a symptom of atherosclerosis, wherein said composition comprises a peptide that is a human apo A-I peptide or an analogue of a human apo A-I peptide wherein said peptide has a first protecting group attached to an amino terminal and a second protecting group attached to a carboxyl terminal and further wherein said peptide comprises a plurality of D amino acid residues.
- 21. The composition of claim 20, wherein said first protecting group and said second protecting group are independently selected from the group consisting of an acetyl, amide, 3 to 20 carbon alkyl groups, Fmoc, t-boc, 9-fluoreneacetyl group, 1-fluorenecarboxylic group, 9-florenecarboxylic group, 9-fluorenone-1-carboxylic group, benzyloxycarbonyl, Xanthyl (Xan), Trityl (Trt), 4-methyltrityl (Mtt), 4-methoxytrityl (Mmt), 4-methoxy-2,3,6-trimethyl-benzenesulphonyl (Mtr), Mesitylene-2-sulphonyl (Mts), 4,4=-dimethoxybenzhydryl (Mbh), Tosyl (Tos), 2,2,5,7,8-pentamethyl chroman-6-sulphonyl (Pmc), 4-methylbenzyl (MeBzl), 4-methoxybenzyl (MeOBzl), Benzyloxy (BzlO), Benzyl (Bzl), Benzoyl (Bz), 3-nitro-2-pyridinesulphenyl (Npys), 1-(4,4-dimentyl-2,6-diaxocyclohexylidene)ethyl (Dde), 2,6-dichlorobenzyl (2,6-DiCl-Bzl), 2-chlorobenzyloxycarbonyl (2-Cl-Z), 2-bromobenzyloxycarbonyl (2-Br-Z), Benzyloxymethyl (Bom), t-butoxycarbonyl (Boc), cyclohexyloxy (cHxO),t-butoxymethyl (Bum), t-butoxy (tBuO), t-Butyl (tBu), Acetyl (Ac), a benzoyl group, a carbobenzoxy group, a propyl group, a butyl group, a pentyl group, a hexyl group group, and Trifluoroacetyl (TFA).
- 22. The composition of claim 20, wherein said first protecting group is an acetyl.
- 23. The composition of claim 20, wherein said second protecting group s an amide.
- 24. The composition of claim 20, wherein more than half of the enantiomeric amino acids comprising said peptide are D amino acids.
- 25. The composition of claim 20, wherein all enantiomeric amino acids comprising said peptide are D amino acids.
- 26. The composition of claim 20, wherein said composition further comprises a pharmaceutically acceptable excipient.
- 27. The composition of claim 26, wherein said excipient is an excipient suitable for oral administration.
- 28. The composition of claim 26, wherein said excipient is an excipient suitable for injection.
- 29. The composition of claim 20, wherein said peptide protects a phospholipid from oxidization by an oxidizing agent.
- 30. The composition of claim 29, wherein said oxidizing agent is selected from the group consisting of hydrogen peroxide, 13(S)-HPODE, 15(S)-HPETE, HPODE, HPETE, HODE, and HETE.
- 31. The composition of claim 29, wherein said phospholipid is selected from the group consisting of 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine (PAPC), 1-stearoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine (SAPC)), 1-stearoyl-2-arachidonyl-sn-glycero-3-phosphorylethanolamine (SAPE).
- 32. A method of ameliorating a symptom of atherosclerosis in a mammal, said method comprising administering to said mammal a peptide or a concatamer of a peptide that:
ranges in length from about 10 to about 30 amino acids; comprises at least one class A amphipathic helix; comprises at least one “D” amino acid residue; protects a phospholipid against oxidation by an oxidizing agent; and is not the D-18A peptide.
- 33. The method of claim 32, wherein said administering comprises orally administering said peptide.
- 34. The method of claim 32, wherein said mammal is a mammal diagnosed as having one or more symptoms of atherosclerosis.
- 35. The method of claim 32, wherein said organism is a mammal diagnosed as at risk for atherosclerosis.
- 36. The method of claim 32, wherein said mammal is a human.
- 37. The method of claim 32, wherein said mammal is non-human mammal.
- 38. The method of claim 32, wherein said peptide further comprises a protecting group coupled to the amino or carboxyl terminus.
- 39. The method of claim 38, wherein said protecting group is a protecting group selected from the group consisting of acetyl, amide, 3 to 20 carbon alkyl groups, Fmoc, t-boc, 9-fluoreneacetyl group, 1-fluorenecarboxylic group, 9-florenecarboxylic group, 9-fluorenone-1-carboxylic group, benzyloxycarbonyl, Xanthyl (Xan), Trityl (Trt), 4-methyltrityl (Mtt), 4-methoxytrityl (Mmt), 4-methoxy-2,3,6-trimethyl-benzenesulphonyl (Mtr), Mesitylene-2-sulphonyl (Mts), 4,4=-dimethoxybenzhydryl (Mbh),Tosyl (Tos), 2,2,5,7,8-pentamethyl chroman-6-sulphonyl (Pmc), 4-methylbenzyl (MeBzl), 4-methoxybenzyl (MeOBzl), Benzyloxy (BzlO), Benzyl (Bzl), Benzoyl (Bz), 3-nitro-2-pyridinesulphenyl (Npys), 1-(4,4-dimentyl-2,6-diaxocyclohexylidene)ethyl (Dde), 2,6-dichlorobenzyl (2,6-DiCl-Bzl), 2-chlorobenzyloxycarbonyl (2-Cl-Z), 2-bromobenzyloxycarbonyl (2-Br-Z), Benzyloxymethyl (Bom), t-butoxycarbonyl (Boc), cyclohexyloxy (cHxO),t-butoxymethyl (Bum), t-butoxy (tBuO), t-Butyl (tBu), Acetyl (Ac), a benzoyl group, a carbobenzoxy group, a propyl group, a butyl group, a pentyl group, a hexyl group group, and Trifluoroacetyl (TFA).
- 40. The method of claim 32, wherein said peptide further comprises a first protecting group coupled to the amino terminus and a second protecting group coupled to the carboxyl terminus.
- 41. The method of claim 32, wherein said peptide has greater than about 50% amino acid sequence identity with human or mouse apo A-1.
- 42. The method of claim 32, wherein said peptide is mixed with a pharmacological excipient.
- 43. The method of claim 32, wherein said peptide is mixed with a pharmacological excipient suitable for oral administration to a mammal.
- 44. The method of claim 32, wherein said peptide comprises an amino acid sequence selected from the group consisting of D-W-L-K-A-F-Y-D-K-V-A-E-K-L-K-E-A-F (SEQ ID NO:2), D-W-F-K-A-F-Y-D-K-V-A-E-K-L-K-E-A-F (SEQ-ID-NO:3), D-W-L-K-A-F-Y-D-K-V-A-E-K-F-K-E-A-F (SEQ-ID-NO:4), D-W-F-K-A-F-Y-D-K-V-A-E-K-F-K-E-A-F(SEQ-ID-NO:5), D-W-L-K-A-F-Y-D-K-F-F-E-K-F-K-E-F-F (SEQ-ID-NO:6), D-W-F-K-A-F-Y-D-K-F-F-E-K-F-K-E-F-F (SEQ-ID-NO:7), D-W-L-K-A-F-Y-D-K-V-A-E-K-F-K-E-A-F (SEQ-ID-NO:8), D-W-L-K-A-F-Y-D-K-V-A-E-K-L-K-E-F-F (SEQ-ID-NO:9), D-W-L-K-A-F-Y-D-K-V-F-E-K-F-K-E-A-F (SEQ-ID-NO:10), D-W-L-K-A-F-Y-D-K-V-F-E-K-L-K-E-F-F (SEQ-ID-NO: 11), D-W-L-K-A-F-Y-D-K-V-A-E-K-F-K-E-F-F (SEQ-ID-NO: 12), D-W-L-K-A-F-Y-D-K-V-F-E-K-F-K-E-F-F (SEQ-ID-NO: 13), E-W-L-K-L-F-Y-E-K-V-L-E-K-F-K-E-A-F (SEQ-ID-NO: 14), E-W-L-K-A-F-Y-D-K-V-A-E-K-F-K-E-A-F (SEQ-ID-NO:15), E-W-L-K-A-F-Y-D-K-V-A-E-K-L-K-E-F-F (SEQ-ID-NO:16), E-W-L-K-A-F-Y-D-K-V-F-E-K-F-K-E-A-F (SEQ-ID-NO: 17), E-W-L-K-A-F-Y-D-K-V-F-E-K-L-K-E-F-F (SEQ-ID-NO: 18), E-W-L-K-A-F-Y-D-K-V-A-E-K-F-K-E-F-F (SEQ-ID-NO:19), E-W-L-K-A-F-Y-D-K-V-F-E-K-F-K-E-F-F (SEQ ID NO:20), and A-F-Y-D-K-V-A-E-K-L-K-E-A-F (SEQ ID NO:21), A-F-Y-D-K-V-A-E-K-F-K-E-A-F (SEQ ID NO:22), A-F-Y-D-K-V-A-E-K-F-K-E-A-F (SEQ ID NO:23), A-F-Y-D-K-F-F-E-K-F-K-E-F-F (SEQ ID NO:24), A-F-Y-D-K-F-F-E-K-F-K-E-F-F (SEQ ID NO:25), A-F-Y-D-K-V-A-E-K-F-K-E-A-F (SEQ ID NO:26), A-F-Y-D-K-V-A-E-K-L-K-E-F-F (SEQ ID NO:27), A-F-Y-D-K-V-F-E-K-F-K-E-A-F (SEQ ID NO:28), A-F-Y-D-K-V-F-E-K-L-K-E-F-F (SEQ ID NO:29), A-F-Y-D-K-V-A-E-K-F-K-E-F-F (SEQ ID NO:30), K-A-F-Y-D-K-V-F-E-K-F-K-E-F (SEQ ID NO:31), L-F-Y-E-K-V-L-E-K-F-K-E-A-F (SEQ ID NO:32), A-F-Y-D-K-V-A-E-K-F-K-E-A-F (SEQ ID NO:33), A-F-Y-D-K-V-A-E-K-L-K-E-F-F (SEQ ID NO:34), A-F-Y-D-K-V-F-E-K-F-K-E-A-F (SEQ ID NO:35), A-F-Y-D-K-V-F-E-K-L-K-E-F-F (SEQ ID NO:36), A-F-Y-D-K-V-A-E-K-F-K-E-F-F (SEQ ID NO:37), A-F-Y-D-K-V-F-E-K-F-K-E-F-F (SEQ ID NO:38), D-W-L-K-A-L-Y-D-K-V-A-E-K-L-K-E-A-L (SEQ ID NO:39), D-W-F-K-A-F-Y-E-K-V-A-E-K-L-K-E-F-F (SEQ ID NO:40), D-W-F-K-A-F-Y-E-K-F-F-E-K-F-K-E-F-F (SEQ ID NO:41), E-W-L-K-A-L-Y-E-K-V-A-E-K-L-K-E-A-L (SEQ ID NO:42), E-W-L-K-A-F-Y-E-K-V-A-E-K-L-K-E-A-F (SEQ ID NO:43), E-W-F-K-A-F-Y-E-K-V-A-E-K-L-K-E-F-F (SEQ ID NO:44), E-W-L-K-A-F-Y-E-K-V-F-E-K-F-K-E-F-F (SEQ ID NO:45), E-W-L-K-A-F-Y-E-K-F-F-E-K-F-K-E-F-F (SEQ ID NO:46), E-W-F-K-A-F-Y-E-K-F-F-E-K-F-K-E-F-F (SEQ ID NO:47), D-F-L-K-A-W-Y-D-K-V-A-E-K-L-K-E-A-W (SEQ ID NO:48), E-F-L-K-A-W-Y-E-K-V-A-E-K-L-K-E-A-W (SEQ ID NO:49), D-F-W-K-A-W-Y-D-K-V-A-E-K-L-K-E-W-W (SEQ ID NO:50), E-F-W-K-A-W-Y-E-K-V-A-E-K-L-K-E-W-W (SEQ ID NO:51), D-K-L-K-A-F-Y-D-K-V-F-E-W-A-K-E-A-F (SEQ ID NO:52), D-K-W-K-A-V-Y-D-K-F-A-E-A-F-K-E-F-L (SEQ ID NO:53), E-K-L-K-A-F-Y-E-K-V-F-E-W-A-K-E-A-F (SEQ ID NO:54), E-K-W-K-A-V-Y-E-K-F-A-E-A-F-K-E-F-L (SEQ ID NO:55), D-W-L-K-A-F-V-D-K-F-A-E-K-F-K-E-A-Y (SEQ ID NO:56), E-K-W-K-A-V-Y-E-K-F-A-E-A-F-K-E-F-L (SEQ ID NO:57), D-W-L-K-A-F-V-Y-D-K-V-F-K-L-K-E-F-F (SEQ ID NO:58), E-W-L-K-A-F-V-Y-E-K-V-F-K-L-K-E-F-F (SEQ ID NO:59), D-W-L-R-A-F-Y-D-K-V-A-E-K-L-K-E-A-F (SEQ ID NO:60), E-W-L-R-A-F-Y-E-K-V-A-E-K-L-K-E-A-F (SEQ ID NO:61), D-W-L-K-A-F-Y-D-R-V-A-E-K-L-K-E-A-F (SEQ ID NO:62), E-W-L-K-A-F-Y-E-R-V-A-E-K-L-K-E-A-F (SEQ ID NO:63), D-W-L-K-A-F-Y-D-K-V-A-E-R-L-K-E-A-F (SEQ ID NO:64), E-W-L-K-A-F-Y-E-K-V-A-E-R-L-K-E-A-F (SEQ ID NO:65), D-W-L-K-A-F-Y-D-K-V-A-E-K-L-R-E-A-F (SEQ ID NO:66), E-W-L-K-A-F-Y-E-K-V-A-E-K-L-R-E-A-F (SEQ ID NO:67), D-W-L-K-A-F-Y-D-R-V-A-E-R-L-K-E-A-F (SEQ ID NO:68), E-W-L-K-A-F-Y-E-R-V-A-E-R-L-K-E-A-F (SEQ ID NO:69), D-W-L-R-A-F-Y-D-K-V-A-E-K-L-R-E-A-F (SEQ ID NO:70), E-W-L-R-A-F-Y-E-K-V-A-E-K-L-R-E-A-F (SEQ ID NO:71), D-W-L-R-A-F-Y-D-R-V-A-E-K-L-K-E-A-F (SEQ ID NO:72), E-W-L-R-A-F-Y-E-R-V-A-E-K-L-K-E-A-F (SEQ ID NO:73), D-W-L-K-A-F-Y-D-K-V-A-E-R-L-R-E-A-F (SEQ ID NO:74), E-W-L-K-A-F-Y-E-K-V-A-E-R-L-R-E-A-F (SEQ ID NO:75), D-W-L-R-A-F-Y-D-K-V-A-E-R-L-K-E-A-F (SEQ ID NO:76), E-W-L-R-A-F-Y-E-K-V-A-E-R-L-K-E-A-F (SEQ ID NO:77), D-W-L-K-A-F-Y-D-K-V-A-E-K-L-K-E-A-F-P-D-W-L-K-A-F-Y-D-K-V-A-E-K-L-K-E-A-F (SEQ ID NO:78), D-W-L-K-A-F-Y-D-K-V-A-E-K-L-K-E-F-F-P-D-W-L-K-A-F-Y-D-K-V-A-E-K-L-K-E-F-F (SEQ ID NO:79), D-W-F-K-A-F-Y-D-K-V-A-E-K-L-K-E-A-F-P-D-W-F-K-A-F-Y-D-K-V-A-E-K-L-K-E-A-F (SEQ ID NO:80), D-K-L-K-A-F-Y-D-K-V-F-E-W-A-K-E-A-F-P-D-K-L-K-A-F-Y-D-K-V-F-E-W-L-K-E-A-F (SEQ ID NO:81), D-K-W-K-A-V-Y-D-K-F-A-E-A-F-K-E-F-L-P-D-K-W-K-A-V-Y-D-K-F-A-E-A-F-K-E-F-L (SEQ ID NO:82), D-W-F-K-A-F-Y-D-K-V-A-E-K-F-K-E-A-F-P-D-W-F-K-A-F-Y-D-K-V-A-E-K-F-K-E-A-F (SEQ ID NO:83), D-W-L-K-A-F-V-Y-D-K-V-F-K-L-K-E-F-F-P-D-W-L-K-A-F-V-Y-D-K-V-F-K-L-K-E-F-F (SEQ ID NO:84), D-W-L-K-A-F-Y-D-K-F-A-E-K-F-K-E-F-F-P-D-W-L-K-A-F-Y-D-K-F-A-E-K-F-K-E-F-F (SEQ ID NO:85).
- 45. The method of claim 44, wherein all enantiomeric amino acids comprising the peptide are D amino acids.
- 46. The method of claim 44, wherein said peptide further comprises a protecting group coupled to the amino or carboxyl terminus.
- 47. The method of claim 46, wherein said protecting group is a protecting group selected from the group consisting of acetyl, CH3—(CH2)n—CO— where n ranges from 1 to 20, and an amide.
- 48. The method of claim 46, wherein said peptide further comprises a first protecting group coupled to the amino terminus and a second protecting group coupled to the carboxyl terminus.
- 49. The method of claim 32, wherein said oxidizing agent is selected from the group consisting of hydrogen peroxide, 13(S)-HPODE, 15(S)-HPETE, HPODE, HPETE, HODE, and HETE.
- 50. The method of claim 32, wherein said phospholipid is selected from the group said phospholipid is selected from the group consisting of 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine (PAPC), 1-stearoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine (SAPC)), 1-stearoyl-2-arachidonyl-sn-glycero-3-phosphorylethanolamine (SAPE).
- 51. A method of ameliorating a symptom of atherosclerosis, said method comprising orally administering to an organism a composition that comprises a peptide that is a human apo A-I peptide or an analogue of a human apo A-I peptide wherein said peptide has a first protecting group attached to an amino terminal and a second protecting group attached to a carboxyl terminal and further wherein said peptide comprises a plurality of D amino acid residues.
- 52. The method of claim 73, wherein said organism is an organism diagnosed as having one or more symptoms of atherosclerosis.
- 53. The method of claim 73, wherein said organism is an organism diagnosed as at risk for atherosclerosis.
- 54. The method of claim 73, wherein said organism is a human.
- 55. The method of claim 73, wherein said organism is non-human mammal.
- 56. The method of claim 73, wherein said first protecting group and said second protecting group are independently selected from the group consisting of an acetyl, a CH3—(CH2)n—CO— where n ranges from 3 to 20, and an amide.
- 57. The method of claim 73, wherein said first protecting group is an acetyl.
- 58. The method of claim 73, wherein said second protecting group is an amide.
- 59. The method of claim 73, wherein said composition further comprises a pharmaceutically acceptable excipient.
- 60. The method of claim 59, wherein said excipient is an excipient suitable for oral administration.
- 61. The method of claim 73, wherein said peptide protects a phospholipid from oxidization by an oxidizing agent.
- 62. The method of claim 61, wherein said oxidizing agent is selected from the group consisting of hydrogen peroxide, 13(S)-HPODE, 15(S)-HPETE, HPODE, HPETE, HODE, and HETE.
- 63. The method of claim 61, wherein said phospholipid is selected from the group consisting of 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine (PAPC), 1-stearoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine (SAPC)), 1-stearoyl-2-arachidonyl-sn-glycero-3-phosphorylethanolamine (SAPE).
- 64. A kit for ameliorating a symptom of atherosclerosis, said kit comprising a container containing a peptide that:
ranges in length from about 10 to about 30 amino acids; comprises at least one class A amphipathic helix; comprises at least one D amino acid residue; protects a phospholipid against oxidation by an oxidizing agent; and is not the 18-A peptide.
- 65. The kit of claim 64, wherein said peptide comprises a peptide having an amino acid sequence selected from the group consisting of D-W-L-K-A-F-Y-D-K-V-A-E-K-L-K-E-A-F (SEQ ID NO:2), D-W-F-K-A-F-Y-D-K-V-A-E-K-L-K-E-A-F (SEQ-ID-NO:3), D-W-L-K-A-F-Y-D-K-V-A-E-K-F-K-E-A-F (SEQ-ID-NO:4), D-W-F-K-A-F-Y-D-K-V-A-E-K-F-K-E-A-F(SEQ-ID-NO:5), D-W-L-K-A-F-Y-D-K-F-F-E-K-F-K-E-F-F (SEQ-ID-NO:6), D-W-F-K-A-F-Y-D-K-F-F-E-K-F-K-E-F-F (SEQ-ID-NO:7), D-W-L-K-A-F-Y-D-K-V-A-E-K-F-K-E-A-F (SEQ-ID-NO:8), D-W-L-K-A-F-Y-D-K-V-A-E-K-L-K-E-F-F (SEQ-ID-NO:9), D-W-L-K-A-F-Y-D-K-V-F-E-K-F-K-E-A-F (SEQ-ID-NO:10), D-W-L-K-A-F-Y-D-K-V-F-E-K-L-K-E-F-F (SEQ-ID-NO: 11), D-W-L-K-A-F-Y-D-K-V-A-E-K-F-K-E-F-F (SEQ-ID-NO: 12), D-W-L-K-A-F-Y-D-K-V-F-E-K-F-K-E-F-F (SEQ-ID-NO: 13), E-W-L-K-L-F-Y-E-K-V-L-E-K-F-K-E-A-F (SEQ-ID-NO:14), E-W-L-K-A-F-Y-D-K-V-A-E-K-F-K-E-A-F (SEQ-ID-NO:15), E-W-L-K-A-F-Y-D-K-V-A-E-K-L-K-E-F-F (SEQ-ID-NO:16), E-W-L-K-A-F-Y-D-K-V-F-E-K-F-K-E-A-F (SEQ-ID-NO:17), E-W-L-K-A-F-Y-D-K-V-F-E-K-L-K-E-F-F (SEQ-ID-NO: 18), E-W-L-K-A-F-Y-D-K-V-A-E-K-F-K-E-F-F (SEQ-ID-NO:19), E-W-L-K-A-F-Y-D-K-V-F-E-K-F-K-E-F-F (SEQ ID NO:20), and A-F-Y-D-K-V-A-E-K-L-K-E-A-F (SEQ ID NO:21), A-F-Y-D-K-V-A-E-K-F-K-E-A-F (SEQ ID NO:22), A-F-Y-D-K-V-A-E-K-F-K-E-A-F (SEQ ID NO:23), A-F-Y-D-K-F-F-E-K-F-K-E-F-F (SEQ ID NO:24), A-F-Y-D-K-F-F-E-K-F-K-E-F-F (SEQ ID NO:25), A-F-Y-D-K-V-A-E-K-F-K-E-A-F (SEQ ID NO:26), A-F-Y-D-K-V-A-E-K-L-K-E-F-F (SEQ ID NO:27), A-F-Y-D-K-V-F-E-K-F-K-E-A-F (SEQ ID NO:28), A-F-Y-D-K-V-F-E-K-L-K-E-F-F (SEQ ID NO:29), A-F-Y-D-K-V-A-E-K-F-K-E-F-F (SEQ ID NO:30), K-A-F-Y-D-K-V-F-E-K-F-K-E-F (SEQ ID NO:31), L-F-Y-E-K-V-L-E-K-F-K-E-A-F (SEQ ID NO:32), A-F-Y-D-K-V-A-E-K-F-K-E-A-F (SEQ ID NO:33), A-F-Y-D-K-V-A-E-K-L-K-E-F-F (SEQ ID NO:34), A-F-Y-D-K-V-F-E-K-F-K-E-A-F (SEQ ID NO:35), A-F-Y-D-K-V-F-E-K-L-K-E-F-F (SEQ ID NO:36), A-F-Y-D-K-V-A-E-K-F-K-E-F-F (SEQ ID NO:37), A-F-Y-D-K-V-F-E-K-F-K-E-F-F (SEQ ID NO:38), D-W-L-K-A-L-Y-D-K-V-A-E-K-L-K-E-A-L (SEQ ID NO:39), D-W-F-K-A-F-Y-E-K-V-A-E-K-L-K-E-F-F (SEQ ID NO:40), D-W-F-K-A-F-Y-E-K-F-F-E-K-F-K-E-F-F (SEQ ID NO:41), E-W-L-K-A-L-Y-E-K-V-A-E-K-L-K-E-A-L (SEQ ID NO:42), E-W-L-K-A-F-Y-E-K-V-A-E-K-L-K-E-A-F (SEQ ID NO:43), E-W-F-K-A-F-Y-E-K-V-A-E-K-L-K-E-F-F (SEQ ID NO:44), E-W-L-K-A-F-Y-E-K-V-F-E-K-F-K-E-F-F (SEQ ID NO:45), E-W-L-K-A-F-Y-E-K-F-F-E-K-F-K-E-F-F (SEQ ID NO:46), E-W-F-K-A-F-Y-E-K-F-F-E-K-F-K-E-F-F (SEQ ID NO:47), D-F-L-K-A-W-Y-D-K-V-A-E-K-L-K-E-A-W (SEQ ID NO:48), E-F-L-K-A-W-Y-E-K-V-A-E-K-L-K-E-A-W (SEQ ID NO:49), D-F-W-K-A-W-Y-D-K-V-A-E-K-L-K-E-W-W (SEQ ID NO:50), E-F-W-K-A-W-Y-E-K-V-A-E-K-L-K-E-W-W (SEQ ID NO:51), D-K-L-K-A-F-Y-D-K-V-F-E-W-A-K-E-A-F (SEQ ID NO:52), D-K-W-K-A-V-Y-D-K-F-A-E-A-F-K-E-F-L (SEQ ID NO:53), E-K-L-K-A-F-Y-E-K-V-F-E-W-A-K-E-A-F (SEQ ID NO:54), E-K-W-K-A-V-Y-E-K-F-A-E-A-F-K-E-F-L (SEQ ID NO:55), D-W-L-K-A-F-V-D-K-F-A-E-K-F-K-E-A-Y (SEQ ID NO:56), E-K-W-K-A-V-Y-E-K-F-A-E-A-F-K-E-F-L (SEQ ID NO:57), D-W-L-K-A-F-V-Y-D-K-V-F-K-L-K-E-F-F (SEQ ID NO:58), E-W-L-K-A-F-V-Y-E-K-V-F-K-L-K-E-F-F (SEQ ID NO:59), D-W-L-R-A-F-Y-D-K-V-A-E-K-L-K-E-A-F (SEQ ID NO:60), E-W-L-R-A-F-Y-E-K-V-A-E-K-L-K-E-A-F (SEQ ID NO:61), D-W-L-K-A-F-Y-D-R-V-A-E-K-L-K-E-A-F (SEQ ID NO:62), E-W-L-K-A-F-Y-E-R-V-A-E-K-L-K-E-A-F (SEQ ID NO:63), D-W-L-K-A-F-Y-D-K-V-A-E-R-L-K-E-A-F (SEQ ID NO:64), E-W-L-K-A-F-Y-E-K-V-A-E-R-L-K-E-A-F (SEQ ID NO:65), D-W-L-K-A-F-Y-D-K-V-A-E-K-L-R-E-A-F (SEQ ID NO:66), E-W-L-K-A-F-Y-E-K-V-A-E-K-L-R-E-A-F (SEQ ID NO:67), D-W-L-K-A-F-Y-D-R-V-A-E-R-L-K-E-A-F (SEQ ID NO:68), E-W-L-K-A-F-Y-E-R-V-A-E-R-L-K-E-A-F (SEQ ID NO:69), D-W-L-R-A-F-Y-D-K-V-A-E-K-L-R-E-A-F (SEQ ID NO:70), E-W-L-R-A-F-Y-E-K-V-A-E-K-L-R-E-A-F (SEQ ID NO:71), D-W-L-R-A-F-Y-D-R-V-A-E-K-L-K-E-A-F (SEQ ID NO:72), E-W-L-R-A-F-Y-E-R-V-A-E-K-L-K-E-A-F (SEQ ID NO:73), D-W-L-K-A-F-Y-D-K-V-A-E-R-L-R-E-A-F (SEQ ID NO:74), E-W-L-K-A-F-Y-E-K-V-A-E-R-L-R-E-A-F (SEQ ID NO:75), D-W-L-R-A-F-Y-D-K-V-A-E-R-L-K-E-A-F (SEQ ID NO:76), E-W-L-R-A-F-Y-E-K-V-A-E-R-L-K-E-A-F (SEQ ID NO:77), D-W-L-K-A-F-Y-D-K-V-A-E-K-L-K-E-A-F-P-D-W-L-K-A-F-Y-D-K-V-A-E-K-L-K-E-A-F (SEQ ID NO:78), D-W-L-K-A-F-Y-D-K-V-A-E-K-L-K-E-F-F-P-D-W-L-K-A-F-Y-D-K-V-A-E-K-L-K-E-F-F (SEQ ID NO:79), D-W-F-K-A-F-Y-D-K-V-A-E-K-L-K-E-A-F-P-D-W-F-K-A-F-Y-D-K-V-A-E-K-L-K-E-A-F (SEQ ID NO:80), D-K-L-K-A-F-Y-D-K-V-F-E-W-A-K-E-A-F-P-D-K-L-K-A-F-Y-D-K-V-F-E-W-L-K-E-A-F (SEQ ID NO:81), D-K-W-K-A-V-Y-D-K-F-A-E-A-F-K-E-F-L-P-D-K-W-K-A-V-Y-D-K-F-A-E-A-F-K-E-F-L (SEQ ID NO:82), D-W-F-K-A-F-Y-D-K-V-A-E-K-F-K-E-A-F-P-D-W-F-K-A-F-Y-D-K-V-A-E-K-F-K-E-A-F (SEQ ID NO:83), D-W-L-K-A-F-V-Y-D-K-V-F-K-L-K-E-F-F-P-D-W-L-K-A-F-V-Y-D-K-V-F-K-L-K-E-F-F (SEQ ID NO:84), D-W-L-K-A-F-Y-D-K-F-A-E-K-F-K-E-F-F-P-D-W-L-K-A-F-Y-D-K-F-A-E-K-F-K-E-F-F (SEQ ID NO:85).
- 66. The kit of claim 64, wherein all enantiomeric amino acids comprising said peptide are D amino acids.
- 67. The kit of claim 64, wherein said peptide is combined with a pharmaceutically acceptable excipient in a unit dosage formulation.
- 68. The kit of claim 67, wherein said unit dosage formulation is for oral administration.
- 69. The kit of claim 64, further comprising instructional materials teaching the use of said peptide for ameliorating one or more symptoms of atherosclerosis.
- 70. A kit for ameliorating a symptom of atherosclerosis, said kit comprising a container containing a composition suitable for oral administration that ameliorates a symptom of atherosclerosis, wherein said composition comprises a peptide that is a human apo A-I peptide or an analogue of a human apo A-I peptide, wherein said peptide has a first protecting group attached to an amino terminal and a second protecting group attached to a carboxyl terminal and further wherein said peptide comprises a plurality of D amino acid residues.
- 71. The kit of claim 70, wherein said peptide is combined with a pharmaceutically acceptable excipient in a unit dosage formulation.
- 72. The kit of claim 70, further comprising instructional materials teaching the use of said peptide for ameliorating one or more symptoms of atherosclerosis.
- 73. A method of mitigating or preventing a coronary complication associated with an acute phase response to an inflammation in a mammal, wherein said coronary complication is a symptom of atherosclerosis, said method comprising administering to a mammal having said acute phase response, or at risk for said acute phase response, a polypeptide of any one of claims 1 through 19.
- 74. The method of claim 73, where said administration is by a route selected from the group consisting of oral administration, nasal administration, rectal administration, intraperitoneal injection, and intravascular injection, subcutaneous injection, transcutaneous administration, and intramuscular injection.
- 75. The method of claim 73, wherein said polypeptide is administered in combination with an all L-form of the same polypeptide.
- 76. The method of claim 73, wherein said polypeptide is provided as a unit formulation in a pharmaceutically acceptable excipient.
- 77. The method of claim 73, wherein said acute phase response is an inflammatory response associated with a recurrent inflammatory disease.
- 78. The method of claim 74, wherein said acute phase response is associated with a disease selected from the group consisting of leprosy, tuberculosis, systemic lupus erythematosus, polymyalgia rheumatica, polyarteritis nodosa, scleroderma, idiopathic pulmonary fibrosis, chronic obstructive pulmonary disease, Alzheimers Disease and AIDS, polymyalgia rheumatica, polyarteritis nodosa, scleroderma, idiopathic pulmonary fibrosis, chronic obstructive pulmonary disease, Alzheimers Disease, AIDS, coronary calcification, calcific aortic stenosis, osteoporosis, and rheumatoid arthritis.
- 79. The method of claim 73, wherein said acute phase response is an inflammatory response associated with a condition selected from the group consisting of a bacterial infection, a viral infection, a fungal infection, an organ transplant, a wound, an implanted prosthesis, parasitic infection, sepsis, endotoxic shock syndrome, and biofilm formation.
- 80. A method of mitigating or preventing a coronary complication associated with an acute phase response to an inflammation in a mammal, wherein said coronary complication is a symptom of atherosclerosis, said method comprising:
assaying said mammal for an acute phase protein (APP) level indicative of an acute phase response or a significant risk of an acute phase response; and administering to a mammal showing an acute phase protein (APP) level indicative of an acute phase response a polypeptide of any one of claims 1 through 19.
- 81. The method of claim 80, wherein said acute phase protein (APP) is a positive APR selected from the group consisting of serum amyloid A, c-reactive protein, serum amyloid P component, C2 complement protein, C3 complement protein, C4 complement protein, C5 complement protein, C9 complement protein, B complement protein, C1 inhibitor, C4 binding protein, fibrinogen, von Willebrand factor, Δ1-antitrypsin, Δ1-antichymotrypsin, Δ2 antiplasmin, heparin cofactor II, plasminogen activator inhibitor I, haptoglobin, haemopexin, ceruloplasmin, manganese superoxide dismutase, Δ1-acid glycoprotein, haeme oxygenase, mannose binding protein, leukocyte protein I, lipoprotein (a), and lipopolysaccharide binding protein.
- 82. The method of claim 80, wherein said acute phase protein (APP) is a negative APR selected from the group consisting of albumin, prealbumin, transferin, apoAI, apoAII, Δ2-HS glycoprotein, inter-Δ-trypsin inhibitor, histidine rich glycoprotein.
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application is a continuation-in-part of U.S. Ser. No. 09/645,454, filed on Aug. 24, 2000, which is incorporated herein by reference in its entirety for all purposes.
STATEMENT AS TO RIGHTS TO INVENTIONS MADE UNDER FEDERALLY SPONSORED RESEARCH AND DEVELOPMENT
[0002] This work was supported by United States Public Health Service and National Heart, Lung, and Blood Institute Grants HL30568 and HL34343. The Government of the United States of America may have certain rights in this invention.
Continuation in Parts (1)
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Number |
Date |
Country |
Parent |
09645454 |
Aug 2000 |
US |
Child |
09896841 |
Jun 2001 |
US |