Peptides and peptide mimetics to treat pathologies characterized by an inflammatory response
View Patent ↗This invention provides novel active agents (e.g. peptides, small organic molecules, amino acid pairs, etc.) peptides that ameliorate one or more symptoms of atherosclerosis and/or other pathologies characterized by an inflammatory response. In certain embodiment, the peptides resemble a G* amphipathic helix of apolipoprotein J. The agents are highly stable and readily administered via an oral route.
1. A peptide that ameliorates a symptom of atherosclerosis, wherein said peptide comprises a retro form of the amino acid sequence 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), wherein said peptide comprises all “L” amino acids.
2. The peptide of claim 1 , wherein said peptide further comprises a protecting group coupled to the amino or carboxyl terminus.
3. 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.
4. The peptide of claim 3 , wherein said first protecting group and said second protecting group are independently selected from the group consisting of acetyl (Ac), amide, a 3 to 20 carbon alkyl group, Fmoc, 9-fluoreneacetyl group, 1-fluorenecarboxylic group, 9-fluorenecarboxylic 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-dimethyl-2,6-dioxocyclohexylidene)ethyl (Dde), 2,6-dichlorobenzyl (2,6-DiCl-Bzl), 2-chlorobenzyloxycarbonyl (2-Cl—Z), 2-bromobenzyloxycarbonyl (2-Br—Z), Benzyloxymethyl (Bom), t-butoxycarbonyl (tBoc), cyclohexyloxy (cHxO),t-butoxymethyl (Bum), t-butoxy (tBuO), t-Butyl (tBu), and Trifluoroacetyl (TFA).
5. The peptide of claim 1 , wherein said peptide is mixed with a pharmacologically acceptable excipient.
6. The peptide of claim 1 , wherein said peptide is mixed with a pharmacologically acceptable excipient suitable for oral administration to a mammal.
7. The peptide of claim 3 , wherein said first protecting group is a protecting group selected from the group consisting of acetyl, propionyl, and a 3 to 20 carbon alkyl.
8. The peptide of claim 3 , wherein said second protecting group is an amide.
9. The peptide of claim 7 , wherein said first protecting group is an acetyl and said second protecting group is an amide.
10. A method of treating a vascular condition and/or a condition characterized by an inflammatory response and/or a condition characterized by the formation of oxidized reactive species in a mammal, said method comprising:
administering to a mammal in need thereof one or more of the peptides according to any one of claims 1 - 4 , and 5 - 9 .
11. A method of ameliorating one or more symptoms of a condition selected from the group consisting of atherosclerosis, said method comprising administering to a mammal in need thereof a peptide according to any one of claims 1 - 4 , and 5 - 9 .
12. A stent for delivering drugs to a vessel in a body, said stent comprising:
a stent framework including a plurality of reservoirs formed therein; and
a peptide according to any one of claims 1 - 4 , and 5 - 9 .
13. A method of manufacturing a drug-polymer stent, said method comprising:
providing a stent framework;
cutting a plurality of reservoirs in the stent framework; and
applying to said reservoirs a composition comprising a peptide according to any one of claims 1 - 4 , and 5 - 9 .
14. A method of treating a vascular condition, said method comprising:
positioning a stent according to claim 12 within a vessel of a body;
expanding the stent; and
eluting said peptide from at least a surface of the stent.