Orally administered small peptides synergize statin activity

Abstract

This invention provides novel peptides that ameliorate one or more symptoms of atherosclerosis. The peptides are highly stable and readily administered via an oral route. The peptides are effective to stimulate the formation and cycling of pre-beta high density lipoprotein-like particles and/or to promote lipid transport and detoxification. This invention also provides a method of tracking a peptide in a mammal. In addition, the peptides inhibit osteoporosis. When administered with a statin, the peptides enhance the activity of the statin permitting the statin to be used at significantly lower dosages and/or cause the statins to be significantly more anti-inflammatory at any given dose.

1 . A peptide that ameliorates one or more symptoms of an inflammatory condition, wherein said peptide: 
 ranges in length from 3 to about 5 amino acids;    is soluble in ethyl acetate at a concentration greater than about 4mg/mL;    is soluble in aqueous buffer at pH 7.0;    when contacted with a phospholipid in an aqueous environment, forms particles with a diameter of approximately 7.5 nm and forms stacked bilayers with a bilayer dimension on the order of 3.4 to 4.1 nm with spacing between the bilayers in the stack of approximately 2 nm;    has a molecular weight less than about 900 daltons;    converts pro-inflammatory HDL to anti-inflammatory HDL or makes anti-inflammatory HDL more anti-inflammatory; and    does not have the amino acid sequence Lys-Arg-Asp-Ser (SEQ ID NO:238) in which Lys-Arg-Asp and Ser are all L amino acids.    
     
     
         2 . The peptide of  claim 1 , wherein said peptide protects a phospholipid against oxidation by an oxidizing agent  
     
     
         3 . The peptide of  claim 2 , wherein said oxidizing agent is selected from the group consisting of hydrogen peroxide, 13(S)—HPODE, 15(S)—HPETE, HPODE, HPETE, HODE, and HETE.  
     
     
         4 . The peptide of  claim 2 , 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)), and 1-stearoyl-2-arachidonyl-sn-glycero-3-phosphorylethanolamine (SAPE).  
     
     
         5 . A peptide that ameliorates one or more symptoms of an inflammatory condition, said peptide having the formula:  
       
         
           
                 
                 
                 
               
                     
                     
                 
                     
                   X 1 -X 2 -X 3   n -X 4   
                     
                 
                     
                     
                 
             
                
                
                
               
            
           
         
       
       wherein: 
 n is 0 or 1;  
 X 1  is a hydrophobic amino acid and/or bears a hydrophobic protecting group;  
 X 4  is a hydrophobic amino acid and/or bears a hydrophobic protecting group; and  
 when n is 0: 
 X 2  is an amino acid selected from the group consisting of an acidic amino acid, a basic amino acid, and a histidine;  
 
 when n is 1: 
 X 2  and X 3  are independently an acidic amino acid, a basic amino acid, an aliphatic amino acid, or an aromatic amino acid such that  
 when X 2  is an acidic amino acid; X 3  is a basic amino acid, an aliphatic amino acid, or an aromatic amino acid;  
 when X 2  is a basic amino acid; X 3  is an acidic amino acid, an aliphatic amino acid, or an aromatic amino acid; and  
 when X 2  is an aliphatic or aromatic amino acid, X 3  is an acidic amino acid, or a basic amino acid;  
 said peptide converts pro-inflammatory HDL to anti-inflammatory HDL or makes anti-inflammatory HDL more anti-inflammatory; and  
 said peptide does not have the amino acid sequence Lys-Arg-Asp-Ser (SEQ ID NO:238) in which Lys-Arg-Asp and Ser are all L amino acids.  
 
 
     
     
         6 . The peptide of  claim 5 , wherein n is 0.  
     
     
         7 . The peptide of  claim 6 , wherein wherein X 1  and X 4  are independently selected from the group consisting of alanine (Ala), valine (Val), leucine (Leu), isoleucine (Ile), proline (Pro) phenylalanine (Phe), tryptophan (Trp), methionine (Met), serine (Ser) bearing a hydrophobic protecting group, beta-naphthyl alanine, alpha-naphthyl alanine, norleucine, cyclohexylalanine, threonine (Thr) bearing a hydrophobic protecting group, tyrosine (Tyr) bearing a hydrophobic protecting group, lysine (Lys) bearing a hydrophobic protecting group, arginine (Arg) bearing a hydrophobic protecting group, omithine (Om) bearing a hydrophobic protecting group, aspartic acid (Asp) bearing a hydrophobic protecting group, cysteine (Cys) bearing a hydrophobic protecting group, and glutamic acid (Glu) bearing a hydrophobic protecting group.  
     
     
         8 . The peptide of  claim 7 , wherein: 
 X 1  is is selected from the group consisting of Glu, Leu, Lys, Orn, Phe, Trp, and norLeu;    X 2  is selected from the group consisting of Asp, Arg, and Glu; and    X 4  is selected from the group consisting of Ser, Thr, Ile, Leu, Trp, Tyr, Phe, and norleu.    
     
     
         9 . The peptide of  claim 7 , wherein 
 X 1  is is selected from the group consisting of Glu, Leu, Lys, Orn, Phe, Trp, and norLeu;    X 2  is selected from the group consisting of Lys, Arg, and His; and    X 4  is selected from the group consisting of Asp, Arg, and Glu.    
     
     
         10 . The peptide of  claim 6  wherein X 1  bears a hydrophobic protecting group.  
     
     
         11 . The peptide of  claim 10 , wherein said hydrophobic protecting group is selected from the group consisting of polyethylene glycol (PEG), t-butoxycarbonyl (Boc), Fmoc, nicotinyl, OtBu, a benzoyl group, an acetyl (Ac), a carbobenzoxy, methyl, ethyl, a propyl, a butyl, a pentyl a hexyl ester, an N-methyl anthranilyl, and a 3 to 20 carbon alkyl, amide, a 3 to 20 carbon alkyl group, 9-fluoreneacetyl group, 1-fluorenecarboxylic group, 9-fluorenecarboxylic group, 9-fluorenone-1-carboxylic group, benzyloxycarbonyl (is also called carbobenzoxy mentioned above), 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), cyclohexyloxy (cHxO),t-butoxymethyl (Bum), t-butoxy (tBuO), t-Butyl (tBu), trifluoroacetyl (TFA), 4[N-{1-(4,4-dimethyl-2,6-dioxocyclohexylidene)-3-methyldibutyl)-amino}benzyl ester (ODmab), α-allyl ester (OAll), 2-phenylisopropyl ester (2-PhiPr), 1-[4,4-dimethyl-2,6-dioxycyclohex-1-yl-idene)ethyl (Dde).  
     
     
         12 . The peptide of  claim 11 , wherein said hydrophobic protecting group is selected from the group consisting of Boc, Fmoc, nicotinyl, and OtBu.  
     
     
         13 . The peptide of  claim 10 , wherein X 4  bears a hydrophobic protecting group.  
     
     
         14 . The peptide of  claim 13 , wherein said hydrophobic protecting group is selected from the group consisting of polyethylene glycol (PEG), t-butoxycarbonyl (Boc), Fmoc, nicotinyl, OtBu, a benzoyl group, an acetyl (Ac), a carbobenzoxy, methyl, ethyl, a propyl, a butyl, a pentyl a hexyl ester, an N-methyl anthranilyl, and a 3 to 20 carbon alkyl, amide, a 3 to 20 carbon alkyl group, 9-fluoreneacetyl group, 1-fluorenecarboxylic group, 9-fluorenecarboxylic group, 9-fluorenone-1-carboxylic group, benzyloxycarbonyl (is also called carbobenzoxy mentioned above), 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), cyclohexyloxy (cHxO), t-butoxymethyl (Bum), t-butoxy (tBuO), t-Butyl (tBu), trifluoroacetyl (TFA), 4[N-{1-(4,4-dimethyl-2,6-dioxocyclohexylidene)-3-methyldibutyl)-amino}benzyl ester (ODmab), α-allyl ester (OAll), 2-phenylisopropyl ester (2-PhiPr), 1-[4,4-dimethyl-2,6-dioxycyclohex-1-yl-idene)ethyl (Dde).  
     
     
         15 . The peptide of  claim 14 , wherein the N-terminus of said peptide is blocked with a protecting group selected from the group consisting of Boc-, Fmoc-, and Nicotinyl-.  
     
     
         16 . The peptide of  claim 14 , wherein the C-terminus of said peptide is blocked with a protecting group selected from the group consisting of tBu, and OtBu.  
     
     
         17 . The peptide of  claim 6 , wherein said peptide comprises the amino acid sequence of a peptide in Table 3.  
     
     
         18 . The peptide of  claim 6 , wherein said peptide is a peptide from Table 3.  
     
     
         19 . The peptide of  claim 6 , wherein said peptide comprises at least one D-amino acid.  
     
     
         20 . The peptide of  claim 6 , wherein said peptide comprises all D-amino acids.  
     
     
         21 . The peptide of  claim 6 , wherein said peptide comprises alternating D- and L-amino acids.  
     
     
         22 . The peptide of  claim 6 , wherein said peptide comprises all L-amino acids.  
     
     
         23 . The peptide of  claim 6 , wherein said peptide is mixed with a pharmacologically acceptable excipient.  
     
     
         24 . The peptide of  claim 6 , wherein said peptide is mixed with a pharmacologically acceptable excipient suitable for oral administration to a mammal.  
     
     
         25 . The peptide of  claim 6 , wherein said polypeptide is provided as a unit formulation in a pharmaceutically acceptable excipient.  
     
     
         26 . The peptide of  claim 6 , wherein said polypeptide is provided as a time release formulation.  
     
     
         27 . The peptide of  claim 6 , wherein said peptide protects a phospholipid against oxidation by an oxidizing agent  
     
     
         28 . The peptide of  claim 27 , wherein said oxidizing agent is selected from the group consisting of hydrogen peroxide, 13(S)—HPODE, 15(S)—HPETE, HPODE, HPETE, HODE, and HETE.  
     
     
         29 . The peptide of  claim 27 , 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).  
     
     
         30 . The peptide of  claim 6 , wherein said peptide is coupled to a biotin.  
     
     
         31 . The peptide of  claim 5 , wherein: 
 n is 1; and    X 2  and X 3  are independently an acidic amino acid or a basic amino acid such that when X 2  is an acidic amino acid, X 3  is a basic amino acid and when X 2  is a basic amino acid, X 3  is an acidic amino acid.    
     
     
         32 . The peptide of  claim 31 , wherein wherein X 1  and X 4  are independently selected from the group consisting of alanine (Ala), valine (Val), leucine (Leu), isoleucine (Ile), proline (Pro), phenylalanine (Phe), tryptophan (Trp), methionine (Met), serine (Ser) bearing a hydrophobic protecting group, beta-naphthyl alanine, alpha-naphthyl alanine, norleucine, cyclohexylalanine, threonine (Thr) bearing a hydrophobic protecting group, tyrosine (Tyr) bearing a hydrophobic protecting group, lysine (Lys) bearing a hydrophobic protecting group, arginine (Arg) bearing a hydrophobic protecting group, omithine (Orn) bearing a hydrophobic protecting group, aspartic acid (Asp) bearing a hydrophobic protecting group, cysteine (Cys) bearing a hydrophobic protecting group, and glutamic acid (Glu) bearing a hydrophobic protecting group.  
     
     
         33 . The peptide of  claim 32 , wherein 
 X 2  and X 3  are independently selected from the group consisting of Asp, Glu, Lys, Arg, and His.    
     
     
         34 . The peptide of  claim 32 , wherein 
 X 2  and X 3  are independently selected from the group consisting of Asp, Arg, and Glu.    
     
     
         35 . The peptide of  claim 33  wherein X 1  bears a hydrophobic protecting group.  
     
     
         36 . The peptide of  claim 35 , wherein said hydrophobic protecting group is selected from the group consisting of polyethylene glycol (PEG), t-butoxycarbonyl (Boc), Fmoc, nicotinyl, OtBu, a benzoyl group, an acetyl (Ac), a carbobenzoxy, methyl, ethyl, a propyl, a butyl, a pentyl a hexyl ester, an N-methyl anthranilyl, and a 3 to 20 carbon alkyl, amide, a 3 to 20 carbon alkyl group, 9-fluoreneacetyl group, 1-fluorenecarboxylic group, 9-fluorenecarboxylic group, 9-fluorenone-1-carboxylic group, benzyloxycarbonyl (is also called carbobenzoxy mentioned above), 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), cyclohexyloxy (cHxO), t-butoxymethyl (Bum), t-butoxy (tBuO), t-Butyl (tBu), trifluoroacetyl (TFA), 4[N-{1-(4,4-dimethyl-2,6-dioxocyclohexylidene)-3-methyldibutyl)-amino}benzyl ester (ODmab), α-allyl ester (OAll), 2-phenylisopropyl ester (2-PhiPr), 1-[4,4-dimethyl-2,6-dioxycyclohex-1-yl-idene)ethyl (Dde).  
     
     
         37 . The peptide of  claim 35 , wherein said said hydrophobic protecting group is selected from the group consisting of Boc, Fmoc, nicotinyl, and OtBu.  
     
     
         38 . The peptide of  claim 35 , wherein X 4  bears a hydrophobic protecting group.  
     
     
         39 . The peptide of  claim 38 , wherein said hydrophobic protecting group is selected from the group consisting of polyethylene glycol (PEG), t-butoxycarbonyl (Boc), Fmoc, nicotinyl, OtBu, a benzoyl group, an acetyl (Ac), a carbobenzoxy, methyl, ethyl, a propyl, a butyl, a pentyl a hexyl ester, an N-methyl anthranilyl, and a 3 to 20 carbon alkyl, amide, a 3 to 20 carbon alkyl group, 9-fluoreneacetyl group, 1-fluorenecarboxylic group, 9-fluorenecarboxylic group, 9-fluorenone-1-carboxylic group, benzyloxycarbonyl (is also called carbobenzoxy mentioned above), 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), cyclohexyloxy (cHxO), t-butoxymethyl (Bum), t-butoxy (tBuO), t-Butyl (tBu), trifluoroacetyl (TFA), 4[N-{1-(4,4-dimethyl-2,6-dioxocyclohexylidene)-3-methyldibutyl)-amino}benzyl ester (ODmab), α-allyl ester (OAll), 2-phenylisopropyl ester (2-PhiPr), 1-[4,4-dimethyl-2,6-dioxycyclohex-1-yl-idene)ethyl (Dde).  
     
     
         40 . The peptide of  claim 35 , wherein the N-terminus of said peptide is blocked with a protecting group selected from the group consisting of Boc-, Fmoc-, and Nicotinyl-.  
     
     
         41 . The peptide of  claim 35 , wherein the C-terminus of said peptide is blocked with a protecting group selected from the group consisting of tBu, and OtBu.  
     
     
         42 . The peptide of  claim 31 , wherein said peptide comprises the amino acid sequence of a peptide in Table 4.  
     
     
         43 . The peptide of  claim 31 , wherein said peptide is a peptide from Table 4.  
     
     
         44 . The peptide of  claim 31 , wherein said peptide comprises at least one D-amino acid.  
     
     
         45 . The peptide of  claim 31 , wherein said peptide comprises all D-amino acids.  
     
     
         46 . The peptide of  claim 31 , wherein said peptide comprises alternating D- and L-amino acids.  
     
     
         47 . The peptide of  claim 31 , wherein said peptide comprises all L-amino acids.  
     
     
         48 . The peptide of  claim 31 , wherein said peptide is mixed with a pharmacologically acceptable excipient.  
     
     
         49 . The peptide of  claim 31 , wherein said peptide is mixed with a pharmacologically acceptable excipient suitable for oral administration to a mammal.  
     
     
         50 . The peptide of  claim 31 , wherein said polypeptide is provided as a unit formulation in a pharmaceutically acceptable excipient.  
     
     
         51 . The peptide of  claim 31 , wherein said polypeptide is provided as a time release formulation.  
     
     
         52 . The peptide of  claim 31 , wherein said peptide protects a phospholipid against oxidation by an oxidizing agent  
     
     
         53 . The peptide of  claim 31 , wherein said peptide is coupled to a biotin.  
     
     
         54 . The peptide of  claim 5 , wherein: 
 n is 1; and    X 2 , X 3  are independently an acidic, a basic, or a aliphatic amino acid with one of X 2  or X 3  being an acidic or a basic amino acid such that: 
 when X 2  is an acidic or a basic amino acid, X 3  is an aliphatic amino acid; and  
 when X 3  is an acid or a basic amino acid, X 2  is an aliphatic amino acid.  
   
     
     
         55 . The peptide of  claim 54 , wherein wherein X 1  and X 4  are independently selected from the group consisting of alanine (Ala), valine (Val), leucine (Leu), isoleucine (Ile), proline (Pro), phenylalanine (Phe), tryptophan (Trp), methionine (Met), serine (Ser) bearing a hydrophobic protecting group, beta-naphthyl alanine, alpha-naphthyl alanine, norleucine, cyclohexylalanine, threonine (Thr) bearing a hydrophobic protecting group, tyrosine (Tyr) bearing a hydrophobic protecting group, lysine (Lys) bearing a hydrophobic protecting group, arginine (Arg) bearing a hydrophobic protecting group, ornithine (Orn) bearing a hydrophobic protecting group, aspartic acid (Asp) bearing a hydrophobic protecting group, cysteine (Cys) bearing a hydrophobic protecting group, and glutamic acid (Glu) bearing a hydrophobic protecting group.  
     
     
         56 . The peptide of  claim 55 , wherein 
 X 2  and X 3  are independently selected from the group consisting of Asp, Arg, Lys, Leu, Ile, and Glu.    
     
     
         57 . The peptide of  claim 55 , wherein Xl bears a hydrophobic protecting group.  
     
     
         58 . The peptide of  claim 57 , wherein said hydrophobic protecting group is selected from the group consisting of polyethylene glycol (PEG), t-butoxycarbonyl (Boc), Fmoc, nicotinyl, OtBu, a benzoyl group, an acetyl (Ac), a carbobenzoxy, methyl, ethyl, a propyl, a butyl, a pentyl a hexyl ester, an N-methyl anthranilyl, and a 3 to 20 carbon alkyl, amide, a 3 to 20 carbon alkyl group, 9-fluoreneacetyl group, 1-fluorenecarboxylic group, 9-fluorenecarboxylic group, 9-fluorenone-1-carboxylic group, benzyloxycarbonyl (is also called carbobenzoxy mentioned above), 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), cyclohexyloxy (cHxO),t-butoxymethyl (Bum), t-butoxy (tBuO), t-Butyl (tBu), trifluoroacetyl (TFA), 4[N-{1-(4,4-dimethyl-2,6-dioxocyclohexylidene)-3-methyldibutyl)-amino}benzyl ester (ODmab), α-allyl ester (OAll), 2-phenylisopropyl ester (2-PhiPr), 1-[4,4-dimethyl-2,6-dioxycyclohex-1-yl-idene)ethyl (Dde).  
     
     
         59 . The peptide of  claim 57 , wherein said said hydrophobic protecting group is selected from the group consisting of Boc, Fmoc, nicotinyl, and OtBu.  
     
     
         60 . The peptide of  claim 57 , wherein X 4  bears a hydrophobic protecting group.  
     
     
         61 . The peptide of  claim 60 , wherein said hydrophobic protecting group is selected from the group consisting of polyethylene glycol (PEG), t-butoxycarbonyl (Boc), Fmoc, nicotinyl, OtBu, a benzoyl group, an acetyl (Ac), a carbobenzoxy, methyl, ethyl, a propyl, a butyl, a pentyl a hexyl ester, an N-methyl anthranilyl, and a 3 to 20 carbon alkyl, amide, a 3 to 20 carbon alkyl group, 9-fluoreneacetyl group, 1-fluorenecarboxylic group, 9-fluorenecarboxylic group, 9-fluorenone-1-carboxylic group, benzyloxycarbonyl (is also called carbobenzoxy mentioned above), 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), cyclohexyloxy (cHxO), t-butoxymethyl (Bum), t-butoxy (tBuO), t-Butyl (tBu), trifluoroacetyl (TFA), 4[N-{1-(4,4-dimethyl-2,6-dioxocyclohexylidene)-3-methyldibutyl)-amino}benzyl ester (ODmab), α-allyl ester (OAll), 2-phenylisopropyl ester (2-PhiPr), 1-[4,4-dimethyl-2,6-dioxycyclohex-1-yl-idene)ethyl (Dde).  
     
     
         62 . The peptide of  claim 57 , wherein the N-terminus of said peptide is blocked with a protecting group selected from the group consisting of Boc-, Fmoc-, and Nicotinyl-.  
     
     
         63 . The peptide of  claim 57 , wherein the C-terminus of said peptide is blocked with a protecting group selected from the group consisting of tBu, and OtBu.  
     
     
         64 . The peptide of  claim 54 , wherein said peptide comprises the amino acid sequence of a peptide in Table 5.  
     
     
         65 . The peptide of  claim 54 , wherein said peptide is a peptide from Table 5.  
     
     
         66 . The peptide of  claim 54 , wherein said peptide comprises at least one D-amino acid.  
     
     
         67 . The peptide of  claim 54 , wherein said peptide comprises all D-amino acids.  
     
     
         68 . The peptide of  claim 54 , wherein said peptide comprises alternating D- and L-amino acids.  
     
     
         69 . The peptide of  claim 54 , wherein said peptide comprises all L-amino acids.  
     
     
         70 . The peptide of  claim 54 , wherein said peptide is mixed with a pharmacologically acceptable excipient.  
     
     
         71 . The peptide of  claim 54 , wherein said peptide is mixed with a pharmacologically acceptable excipient suitable for oral administration to a mammal.  
     
     
         72 . The peptide of  claim 54 , wherein said polypeptide is provided as a unit formulation in a pharmaceutically acceptable excipient.  
     
     
         73 . The peptide of  claim 54 , wherein said polypeptide is provided as a time release formulation.  
     
     
         74 . The peptide of  claim 54 , wherein said peptide protects a phospholipid against oxidation by an oxidizing agent  
     
     
         75 . The peptide of  claim 54 , wherein said peptide is coupled to a biotin.  
     
     
         76 . The peptide of  claim 5 , wherein: 
 n is 1; and    X 2 , X 3  are independently an acidic, a basic, or an aromatic amino acid with one of X 2  or X 3  being an acidic or a basic amino acid such that: 
 when X 2  is an acidic or a basic amino acid, X 3  is an aromatic amino acid; and  
 when X 3  is an acid or a basic amino acid, X 2  is an aromatic amino acid.  
   
     
     
         77 . The peptide of  claim 76 , wherein wherein X 1  and X 4  are independently selected from the group consisting of alanine (Ala), valine (Val), leucine (Leu), isoleucine (Ile), proline (Pro), phenylalanine (Phe), tryptophan (Trp), methionine (Met), serine (Ser) bearing a hydrophobic protecting group, beta-naphthyl alanine, alpha-naphthyl alanine, norleucine, cyclohexylalanine, threonine (Thr) bearing a hydrophobic protecting group, tyrosine (Tyr) bearing a hydrophobic protecting group, lysine (Lys) bearing a hydrophobic protecting group, arginine (Arg) bearing a hydrophobic protecting group, ornithine (Orn) bearing a hydrophobic protecting group, aspartic acid (Asp) bearing a hydrophobic protecting group, cysteine (Cys) bearing a hydrophobic protecting group, and glutamic acid (Glu) bearing a hydrophobic protecting group.  
     
     
         78 . The peptide of  claim 77 , wherein 
 X 2  and X 3  are independently is selected from the group consisting of Asp, Arg, Glu, Trp, Tyr, Phe, and Lys.    
     
     
         79 . The peptide of  claim 76 , wherein X 1  bears a hydrophobic protecting group.  
     
     
         80 . The peptide of  claim 79 , wherein said hydrophobic protecting group is selected from the group consisting of polyethylene glycol (PEG), t-butoxycarbonyl (Boc), fmoc, nicotinyl, OtBu, a benzoyl group, an acetyl (Ac), a carbobenzoxy, methyl, ethyl, a propyl, a butyl, a pentyl a hexyl ester, an N-methyl anthranilyl, and a 3 to 20 carbon alkyl, amide, a 3 to 20 carbon alkyl group, 9-fluoreneacetyl group, 1-fluorenecarboxylic group, 9-fluorenecarboxylic group, 9-fluorenone-1-carboxylic group, benzyloxycarbonyl (is also called carbobenzoxy mentioned above), 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), cyclohexyloxy (cHxO),t-butoxymethyl (Bum), t-butoxy (tBuO), t-Butyl (tBu), trifluoroacetyl (TFA), 4[N-{1-(4,4-dimethyl-2,6-dioxocyclohexylidene)-3-methyldibutyl)-amino}benzyl ester (ODmab), α-allyl ester (OAll), 2-phenylisopropyl ester (2-PhiPr), 1-[4,4-dimethyl-2,6-dioxycyclohex-1-yl-idene)ethyl (Dde).  
     
     
         81 . The peptide of  claim 79 , wherein said said hydrophobic protecting group is selected from the group consisting of Boc, Fmoc, nicotinyl, and OtBu.  
     
     
         82 . The peptide of  claim 79 , wherein X 4  bears a hydrophobic protecting group.  
     
     
         83 . The peptide of  claim 82 , wherein said hydrophobic protecting group is selected from the group consisting of polyethylene glycol (PEG), t-butoxycarbonyl (Boc), Fmoc, nicotinyl, OtBu, a benzoyl group, an acetyl (Ac), a carbobenzoxy, methyl, ethyl, a propyl, a butyl, a pentyl a hexyl ester, an N-methyl anthranilyl, and a 3 to 20 carbon alkyl, amide, a 3 to 20 carbon alkyl group, 9-fluoreneacetyl group, 1-fluorenecarboxylic group, 9-fluorenecarboxylic group, 9-fluorenone-1-carboxylic group, benzyloxycarbonyl (is also called carbobenzoxy mentioned above), 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), cyclohexyloxy (cHxO), t-butoxymethyl (Bum), t-butoxy (tBuO), t-Butyl (tBu), trifluoroacetyl (TFA), 4[N-{1-(4,4-dimethyl-2,6-dioxocyclohexylidene)-3-methyldibutyl)-amino}benzyl ester (ODmab), α-allyl ester (OAll), 2-phenylisopropyl ester (2-PhiPr), 1-[4,4-dimethyl-2,6-dioxycyclohex-1-yl-idene)ethyl (Dde).  
     
     
         84 . The peptide of  claim 79 , wherein the N-terminus of said peptide is blocked with a protecting group selected from the group consisting of Boc-, Fmoc-, and Nicotinyl-.  
     
     
         85 . The peptide of  claim 79 , wherein the C-terminus of said peptide is blocked with a protecting group selected from the group consisting of tBu, and OtBu.  
     
     
         86 . The peptide of  claim 76 , wherein said peptide comprises the amino acid sequence of a peptide in Table 6.  
     
     
         87 . The peptide of  claim 76 , wherein said peptide is a peptide from Table 6.  
     
     
         88 . The peptide of  claim 76 , wherein said peptide comprises at least one D-amino acid.  
     
     
         89 . The peptide of  claim 76 , wherein said peptide comprises all D-amino acids.  
     
     
         90 . The peptide of  claim 76 , wherein said peptide comprises alternating D- and L-amino acids.  
     
     
         91 . The peptide of  claim 76 , wherein said peptide comprises all L-amino acids.  
     
     
         92 . The peptide of  claim 76 , wherein said peptide is mixed with a pharmacologically acceptable excipient.  
     
     
         93 . The peptide of  claim 76 , wherein said peptide is mixed with a pharmacologically acceptable excipient suitable for oral administration to a mammal.  
     
     
         94 . The peptide of  claim 76 , wherein said polypeptide is provided as a unit formulation in a pharmaceutically acceptable excipient.  
     
     
         95 . The peptide of  claim 76 , wherein said polypeptide is provided as a time release formulation.  
     
     
         96 . The peptide of  claim 76 , wherein said peptide protects a phospholipid against oxidation by an oxidizing agent  
     
     
         97 . The peptide of  claim 76 , wherein said peptide is coupled to a biotin.  
     
     
         98 . A peptide that ameliorates one or more symptoms of an inflammatory condition, said peptide having the formula:  
       
         
           
                 
                 
                 
               
                     
                     
                 
                     
                   X 1 -X 2 -X 3 -X 4 -X 5   
                     
                 
                     
                     
                 
             
                
                
                
               
            
           
         
       
       wherein: 
 X 1  is a hydrophobic amino acid and/or bears a hydrophobic protecting group;  
 X 5  is a hydrophobic amino acid and/or bears a hydrophobic protecting group; and  
 X 2 , X 3 , and X 4  are independently selected aromatic amino acids or histidine; and  
 said peptide converts pro-inflammatory HDL to anti-inflammatory HDL or makes anti-inflammatory HDL more anti-inflammatory.  
 
     
     
         99 . The peptide of  claim 98 , wherein wherein X 1  and X 5  are independently selected from the group consisting of alanine (Ala), valine (Val), leucine (Leu), isoleucine (Ile), proline (Pro), phenylalanine (Phe), tryptophan (Trp), methionine (Met), phenylalanine (Phe), tryptophan (Trp), methionine (Met), serine (Ser) bearing a hydrophobic protecting group, beta-naphthyl alanine, alpha-naphthyl alanine, norleucine, cyclohexylalanine, threonine (Thr) bearing a hydrophobic protecting group, tyrosine (Tyr) bearing a hydrophobic protecting group, lysine (Lys) bearing a hydrophobic protecting group, arginine (Arg) bearing a hydrophobic protecting group, ornithine (Orn) bearing a hydrophobic protecting group, aspartic acid (Asp) bearing a hydrophobic protecting group, cysteine (Cys) bearing a hydrophobic protecting group, and glutamic acid (Glu) bearing a hydrophobic protecting group.  
     
     
         100 . The peptide of  claim 99 , wherein 
 X 2 , X 3 , and X 4  are independently is selected from the group consisting of Phe, Val, Trp, Tyr, and His.    
     
     
         101 . The peptide of  claim 98 , wherein Xl bears a hydrophobic protecting group.  
     
     
         102 . The peptide of  claim 101 , wherein said hydrophobic protecting group is selected from the group consisting of polyethylene glycol (PEG), t-butoxycarbonyl (Boc), Fmoc, nicotinyl, OtBu, a benzoyl group, an acetyl (Ac), a carbobenzoxy, methyl, ethyl, a propyl, a butyl, a pentyl a hexyl ester, an N-methyl anthranilyl, and a 3 to 20 carbon alkyl, amide, a 3 to 20 carbon alkyl group, 9-fluoreneacetyl group, 1-fluorenecarboxylic group, 9-fluorenecarboxylic group, 9-fluorenone-1-carboxylic group, benzyloxycarbonyl (is also called carbobenzoxy mentioned above), 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), cyclohexyloxy (cHxO),t-butoxymethyl (Bum), t-butoxy (tBuO), t-Butyl (tBu), trifluoroacetyl (TFA), 4[N-{1-(4,4-dimethyl-2,6-dioxocyclohexylidene)-3-methyldibutyl)-amino}benzyl ester (ODmab), α-allyl ester (OAll), 2-phenylisopropyl ester (2-PhiPr), 1-[4,4-dimethyl-2,6-dioxycyclohex-1-yl-idene)ethyl (Dde).  
     
     
         103 . The peptide of  claim 101 , wherein said said hydrophobic protecting group is selected from the group consisting of Boc, Fmoc, nicotinyl, and OtBu.  
     
     
         104 . The peptide of  claim 101 , wherein X 5  bears a hydrophobic protecting group.  
     
     
         105 . The peptide of  claim 104 , wherein said hydrophobic protecting group is selected from the group consisting of polyethylene glycol (PEG), t-butoxycarbonyl (Boc), Fmoc, nicotinyl, OtBu, a benzoyl group, an acetyl (Ac), a carbobenzoxy, methyl, ethyl, a propyl, a butyl, a pentyl a hexyl ester, an N-methyl anthranilyl, and a 3 to 20 carbon alkyl, amide, a 3 to 20 carbon alkyl group, 9-fluoreneacetyl group, 1-fluorenecarboxylic group, 9-fluorenecarboxylic group, 9-fluorenone-1-carboxylic group, benzyloxycarbonyl (is also called carbobenzoxy mentioned above), 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-CI-Z), 2-bromobenzyloxycarbonyl (2-Br-Z), benzyloxymethyl (Bom), cyclohexyloxy (cHxO), t-butoxymethyl (Bum), t-butoxy (tBuO), t-Butyl (tBu), trifluoroacetyl (TFA), 4[N-{1-(4,4-dimethyl-2,6-dioxocyclohexylidene)-3-methyldibutyl)-amino}benzyl ester (ODmab), α-allyl ester (OAll), 2-phenylisopropyl ester (2-PhiPr), 1-[4,4-dimethyl-2,6-dioxycyclohex-1-yl-idene)ethyl (Dde).  
     
     
         106 . The peptide of  claim 98 , wherein the N-terminus of said peptide is blocked with a protecting group selected from the group consisting of Boc-, Fmoc-, and Nicotinyl-.  
     
     
         107 . The peptide of  claim 98 , wherein the C-terminus of said peptide is blocked with a protecting group selected from the group consisting of tBu, and OtBu.  
     
     
         108 . The peptide of  claim 98 , wherein said peptide comprises the amino acid sequence of a peptide in Table 7.  
     
     
         109 . The peptide of  claim 98 , wherein said peptide is a peptide from Table 7.  
     
     
         110 . The peptide of  claim 98 , wherein said peptide comprises at least one D-amino acid.  
     
     
         111 . The peptide of  claim 98 , wherein said peptide comprises all D-amino acids.  
     
     
         112 . The peptide of  claim 98 , wherein said peptide comprises alternating D- and L-amino acids.  
     
     
         113 . The peptide of  claim 98 , wherein said peptide comprises all L-amino acids.  
     
     
         114 . The peptide of  claim 98 , wherein said peptide is mixed with a pharmacologically acceptable excipient.  
     
     
         115 . The peptide of  claim 98 , wherein said peptide is coupled to a biotin.  
     
     
         116 . A peptide that ameliorates one or more symptoms of an inflammatory condition, wherein said peptide: 
 ranges in length from 5 to 11 amino acids;    the terminal amino acids are hydrophobic amino acids and/or bear hydrophobic protecting groups;    the non-terminal amino acids form at least one acidic domain and at least one basic domain; and    said peptide converts pro-inflammatory HDL to anti-inflammatory HDL or makes anti-inflammatory HDL more anti-inflammatory.    
     
     
         117 . A peptide that ameliorates one or more symptoms of an inflammatory condition, wherein said peptide: 
 ranges in length from 5 to 11 amino acids;    the terminal amino acids are hydrophobic amino acids and/or bear hydrophobic protecting groups;    the non-terminal amino acids form at least one acidic domain or one basic domain and at least one aliphatic domain; and    said peptide converts pro-inflammatory HDL to anti-inflammatory HDL or makes anti-inflammatory HDL more anti-inflammatory.    
     
     
         118 . A peptide that ameliorates one or more symptoms of an inflammatory condition, wherein said peptide: 
 ranges in length from 5 to 11 amino acids;    the terminal amino acids are hydrophobic amino acids and/or bear hydrophobic protecting groups;    the non-terminal amino acids form at least one acidic domain or one basic domain and at least one aromatic domain; and    said peptide converts pro-inflammatory HDL to anti-inflammatory HDL or makes anti-inflammatory HDL more anti-inflammatory.    
     
     
         119 . A peptide that ameliorates one or more symptoms of an inflammatory condition, wherein said peptide: 
 ranges in length from 6 to 11 amino acids;    the terminal amino acids are hydrophobic amino acids and/or bear hydrophobic protecting groups;    the non-terminal amino acids form at least one aromatic domain or two or more aromatic domains separated by one or more histidines; and    said peptide converts pro-inflammatory HDL to anti-inflammatory HDL or makes anti-inflammatory HDL more anti-inflammatory.    
     
     
         120 . A pair of amino acids that ameliorates one or more symptoms of an inflammatory condition, wherein said pair of amino aicds comprise: 
 a first amino acid bearing at least one protecting group; and    a second amino acid bearing at least one protecting group;    wherein said first amino acid and said second amino acid are different species of amino acid, and wherein said pair of amino acids converts pro-inflammatory HDL to anti-inflammatory HDL or makes anti-inflammatory HDL more anti-inflammatory    
     
     
         121 . The pair of amino acids of  claim 120 , wherein said pair of amino acids, when contacted with a phospholipid in an aqueous environment, forms particles with a diameter of approximately 7.5 nm and forms stacked bilayers with a bilayer dimension on the order of 3.4 to 4.1 nm with spacing between the bilayers in the stack of approximately 2 nm.  
     
     
         122 . The pair of amino acids of  claim 120 , wherein said first and second amino acids are independently selected from the group consisting of an acidic amino acid, a basic amino acid, and a non-polar amino acid.  
     
     
         123 . The pair of amino acids of  claim 122 , wherein said first amino acid is acidic or basic and said second amino acid is non-polar, or said first amino acid is non-polar and said second amino acid is acidic or basic.  
     
     
         124 . The pair of amino acids of  claim 122 , wherein both amino acids are acidic.  
     
     
         125 . The pair of amino acids of  claim 122 , wherein both amino acids are basic.  
     
     
         126 . The pair of amino acids of  claim 120 , wherein said pair of amino acids are covalently coupled together directly or through a linker.  
     
     
         127 . The pair of amino acids of  claim 126 , wherein the amino acids are joined through a peptide linkage thereby forming a dipeptide.  
     
     
         128 . The pair of amino acids of  claim 120 , wherein said pair of amino acids are mixed together, but not covalently linked.  
     
     
         129 . The pair of amino acids of  claim 120 , wherein said protecting group is selected from the group consisting of polyethylene glycol (PEG), t-butoxycarbonyl (Boc), Fmoc, nicotinyl, OtBu, a benzoyl group, an acetyl (Ac), a carbobenzoxy, methyl, ethyl, a propyl, a butyl, a pentyl a hexyl ester, an N-methyl anthranilyl, and a 3 to 20 carbon alkyl, amide, a 3 to 20 carbon alkyl group, 9-fluoreneacetyl group, 1-fluorenecarboxylic group, 9-fluorenecarboxylic group, 9-fluorenone-1-carboxylic group, benzyloxycarbonyl (is also called carbobenzoxy mentioned above), 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), cyclohexyloxy (cHxO),t-butoxymethyl (Bum), t-butoxy (tBuO), t-Butyl (tBu), trifluoroacetyl (TFA), 4[N-{1-(4,4-dimethyl-2,6-dioxocyclohexylidene)-3-methyldibutyl)-amino}benzyl ester (ODmab), α-allyl ester (OAll), 2-phenylisopropyl ester (2-PhiPr), 1-[4,4-dimethyl-2,6-dioxycyclohex-1-yl-idene)ethyl (Dde).  
     
     
         130 . The pair of amino acids of  claim 120 , wherein the first amino acid is blocked with a protecting group selected from the group consisting of Boc-, Fmoc-, and nicotinyl-, and the second amino acid is blocked with a protecting group selected from the group consisting of tBu, and OtBu.  
     
     
         131 . The pair of amino acids of  claim 128 , wherein each amino acid bears at least two protecting groups.  
     
     
         132 . The pair of amino acids where each amino acid is blocked with a with a first protecting group selected from the group consisting of Boc-, Fmoc-, and nicotinyl-, and a second protecting group selected from the group consisting of tBu, and OtBu.  
     
     
         133 . The pair of amino acids where each amino acid is blocked with a Boc and an OtBu.  
     
     
         134 . The pair of amino acids of  claim 120 , wherein the pair of amino acids form a dipeptide selected from the group consisting of Phe-Arg, Glu-Leu, and Arg-Glu.  
     
     
         135 . The pair of amino acids of  claim 120 , wherein the pair of amino acids form a dipeptide selected from the group consisting of Boc-Arg-OtBu, Boc-Glu-OtBu, Boc-Phe-Arg-OtBu, Boc-Glu-Leu-OtBu, and Boc-Arg-Glu-OtBu.  
     
     
         136 . A pharmaceutical formulation comprising: 
 one or more peptides according to claims  1 ,  5 ,  6 ,  31 ,  54 ,  76 ,  98 ,  116 ,  117 , and  119 , or a pair of amino acids according to  claim 120;  and    a pharmaceutically acceptable excipient.    
     
     
         137 . The pharmaceutical formulation of  claim 136 , wherein the peptide is present in an effective dose.  
     
     
         138 . The pharmaceutical formulation of  claim 136 , wherein the peptide is in a time release formulation.  
     
     
         139 . The pharmaceutical formulation of  claim 136 , wherein the formulation is formulated as a unit dosage formulation.  
     
     
         140 . The pharmaceutical formulation of  claim 136 , wherein the formulation is formulated for oral administration.  
     
     
         141 . The pharmaceutical formulation of  claim 136 , wherein the formulation is formulated for administration by a route selected from the group consisting of oral administration, inhalation, rectal administration, intraperitoneal injection, intravascular injection, subcutaneous injection, transcutaneous administration, inhalation administration, and intramuscular injection.  
     
     
         142 . A kit comprising: 
 a container containing one or more of the peptides according to claims  1 ,  5 ,  6 ,  31 ,  54 ,  76 ,  98 ,  116 ,  117 , and  119 , or a pair of amino acids according to  claim 120;  and    instructional materials teaching the use of the peptide(s) or pairs of amino acids in the treatment of a pathology characterized by inflammation.    
     
     
         143 . The kit of  claim 142 , wherein said pathology is a pathology selected from the group consisting of atherosclerosis, rheumatoid arthritis, lupus erythematous, polyarteritis nodosa, osteoporosis, Altzheimer's disease, chronic obstructive pulmonary disease, asthma, multiple sclerosis, diabetes, and a viral illnesses.  
     
     
         144 . A method of mitigating one or more symptoms of atherosclerosis in a mammal, said method comprising administering to said mammal an effective amount of the peptide of claims  1 ,  5 ,  6 ,  31 ,  54 ,  76 ,  98 ,  116 ,  117 , and  119 , or a pair of amino acids according to  claim 120 .  
     
     
         145 . The method of  claim 144 , wherein said peptide is in a pharmaceutically acceptable excipient.  
     
     
         146 . The method of  claim 144 , wherein said peptide is administered in conjunction with a lipid.  
     
     
         147 . The method of  claim 144 , wherein said peptide is in a pharmaceutically acceptable excipient suitable for oral administration.  
     
     
         148 . The method of  claim 144 , wherein said peptide is administered as a unit dosage formulation.  
     
     
         149 . The method of  claim 144 , wherein said administering comprises administering said peptide by a route selected from the group consisting of oral administration, inhalation, rectal administration, intraperitoneal injection, intravascular injection, subcutaneous injection, transcutaneous administration, and intramuscular injection.  
     
     
         150 . The method of  claim 144 , wherein said mammal is a mammal diagnosed as having one or more symptoms of atherosclerosis.  
     
     
         151 . The method of  claim 144 , wherein said mammal is a mammal diagnosed as at risk for stroke or atherosclerosis.  
     
     
         152 . The method of  claim 144 , wherein said mammal is a human.  
     
     
         153 . The method of  claim 144 , wherein said mammal is non-human mammal.  
     
     
         154 . A method of mitigating one or more symptoms of an inflammatory pathology, , said method comprising administering to said mammal an effective amount of the peptide of claims  1 ,  5 ,  6 ,  31 ,  54 ,  76 ,  98 ,  116 ,  117 , and  119 , or a pair of amino acids according to  claim 120 .  
     
     
         155 . The method of  claim 154 , wherein said inflammatory pathology is a pathology selected from the group consisting of atherosclerosis, rheumatoid arthritis, lupus erythematous, polyarteritis nodosa, osteoporosis, Altzheimer's disease, multiple sclerosis, chronic obstructive pulmonary disease, asthma, diabetes, and a viral illnesses.  
     
     
         156 . The method of  claim 154 , wherein said peptide is in a pharmaceutically acceptable excipient.  
     
     
         157 . The method of  claim 154 , wherein said peptide is administered in conjunction with a lipid.  
     
     
         158 . The method of  claim 154 , wherein said peptide is in a pharmaceutically acceptable excipient suitable for oral administration.  
     
     
         159 . The method of  claim 154 , wherein said peptide is administered as a unit dosage formulation.  
     
     
         160 . The method of  claim 154 , wherein said administering comprises administering said peptide by a route selected from the group consisting of oral administration, inhalation, rectal administration, intraperitoneal injection, intravascular injection, subcutaneous injection, transcutaneous administration, and intramuscular injection.  
     
     
         161 . The method of  claim 154 , wherein said mammal is a mammal diagnosed as at risk for stroke.  
     
     
         162 . The method of  claim 154 , wherein said mammal is a human.  
     
     
         163 . The method of  claim 154 , wherein said mammal is non-human mammal.  
     
     
         164 . A method of enhancing the activity of a statin in a mammal, said method comprising coadministering with said statin an effective amount of the peptide of claims  1 ,  5 ,  6 ,  31 ,  54 ,  76 ,  98 ,  116 ,  117 , and  119 , or a pair of amino acids according to  claim 120;   
     
     
         165 . The method of  claim 164 , wherein said statin is selected from the group consisting of cerivastatin, atorvastatin, simvastatin, pravastatin, fluvastatin, lovastatin. rosuvastatin, and pitavastatin.  
     
     
         166 . The method of  claim 164 , wherein said peptide is administered simultaneously with said statin.  
     
     
         167 . The method of  claim 164 , wherein said peptide is administered before said statin.  
     
     
         168 . The method of  claim 164 , wherein said peptide is administered after said statin.  
     
     
         169 . The method of  claim 164 , wherein said peptide and/or said statin are administered as a unit dosage formulation.  
     
     
         170 . The method of  claim 164 , wherein said administering comprises administering said peptide and/or said statin by a route selected from the group consisting of oral administration, inhalation, rectal administration, intraperitoneal injection, intravascular injection, subcutaneous injection, transcutaneous administration, and intramuscular injection.  
     
     
         171 . The method of  claim 164 , wherein said mammal is a mammal diagnosed as having one or more symptoms of atherosclerosis.  
     
     
         172 . The method of  claim 164 , wherein said mammal is a mammal diagnosed as at risk for stroke or atherosclerosis.  
     
     
         173 . The method of  claim 164 , wherein said mammal is a human.  
     
     
         174 . The method of  claim 164 , wherein said mammal is non-human mammal.  
     
     
         175 . A method of mitigating one or more symptoms associated with atherosclerosis in a mammal, said method comprising: 
 administering to said mammal an effective amount of a statin; and    an effective amount of a peptide of claims  1 ,  5 ,  6 ,  31 ,  54 ,  76 ,  98 ,  116 ,  117 , and  119 , or a pair of amino acids according to  claim 120;     wherein the effective amount of the statin is lower than the effective amount of a statin administered without said peptide.    
     
     
         176 . The method of  claim 175 , wherein the effective amount of the peptide is lower than the effective amount of the peptide administered without said statin.  
     
     
         177 . The method of  claim 175 , wherein said statin is selected from the group consisting of cerivastatin, atorvastatin, simvastatin, pravastatin, fluvastatin, lovastatin. rosuvastatin, and pitavastatin.  
     
     
         178 . The method of  claim 175 , wherein said peptide is administered simultaneously with said statin.  
     
     
         179 . The method of  claim 175 , wherein said peptide is administered before said statin.  
     
     
         180 . The method of  claim 175 , wherein said peptide is administered after said statin.  
     
     
         181 . The method of  claim 175 , wherein said peptide and/or said statin are administered as a unit dosage formulation.  
     
     
         182 . The method of  claim 175 , wherein said administering comprises orally administering said composition.  
     
     
         183 . The method of  claim 175 , wherein said administering is by a route selected from the group consisting of oral administration, inhalation, rectal administration, intraperitoneal injection, intravascular injection, subcutaneous injection, transcutaneous administration, inhalation administration, and intramuscular injection.  
     
     
         184 . The method of  claim 175 , wherein said mammal is a mammal diagnosed as having one or more symptoms of atherosclerosis.  
     
     
         185 . The method of  claim 175 , wherein said mammal is a mammal diagnosed as at risk for stroke or atherosclerosis.  
     
     
         186 . The method of  claim 175 , wherein said mammal is a human.  
     
     
         187 . The method of  claim 175 , wherein said mammal is non-human mammal.  
     
     
         188 . A pharmaceutical formulation, the formulation comprising: 
 a statin and/or Ezetimibe; and    a peptide or a concatamer of a peptide according to any of claims  1 ,  5 ,  6 ,  31 ,  54 ,  76 ,  98 ,  116 ,  117 , and  119 , or a pair of amino acids according to  claim 120 .    
     
     
         189 . The pharmaceutical formulation of  claim 188 , wherein the peptide and/or the statin are present in an effective dose.  
     
     
         190 . The pharmaceutical formulation of  claim 189 , wherein the effective amount of the statin is lower than the effective amount of the statin administered without the peptide.  
     
     
         191 . The pharmaceutical formulation of  claim 189 , wherein the effective amount of the peptide is lower than the effective amount of the peptide administered without the statin.  
     
     
         192 . The pharmaceutical formulation of  claim 189 , wherein the effective amount of the Ezetimibe is lower than the effective amount of the Ezetimibe administered without the peptide.  
     
     
         193 . The pharmaceutical formulation of  claim 189 , wherein the effective amount of the peptide is lower than the effective amount of the peptide administered without the Ezetimibe.  
     
     
         194 . The pharmaceutical formulation of  claim 188 , wherein the statin is selected from the group consisting of cerivastatin, atorvastatin, simvastatin, pravastatin, fluvastatin, lovastatin. rosuvastatin, and pitavastatin.  
     
     
         195 . The pharmaceutical formulation of  claim 188 , wherein the Ezetimibe, the statin, and/or the peptide are in a time release formulation.  
     
     
         196 . The pharmaceutical formulation of  claim 188 , wherein the formulation is formulated as a unit dosage formulation.  
     
     
         197 . The pharmaceutical formulation of  claim 188 , wherein the formulation is formulated for oral administration.  
     
     
         198 . The pharmaceutical formulation of  claim 188 , wherein the formulation is formulated for administration by a route selected from the group consisting of oral administration, inhalation, rectal administration, intraperitoneal injection, intravascular injection, subcutaneous injection, transcutaneous administration, inhalation administration, and intramuscular injection.  
     
     
         199 . The pharmaceutical formulation of  claim 188 , wherein the formulation further comprises one or more phospholipids.  
     
     
         200 . A method of reducing or inhibiting one or more symptoms of osteoporosis in a mammal, the method comprising administering to the mammal one or more peptide according to claims  1 ,  5 ,  6 ,  31 ,  54 ,  76 ,  98 ,  116 ,  117 , and  119 , or a pair of amino acids according to  claim 120 , wherein the peptide or pair of amino acids is administered in a concentration sufficient to reduce or eliminate one or more symptoms of osteoporosis.  
     
     
         201 . The method of  claim 200 , wherein the peptide is administered in a concentration sufficient to reduce or eliminate decalcification of a bone.  
     
     
         202 . The method of  claim 200 , wherein the peptide is administered in a concentration sufficient to induce recalcification of a bone.  
     
     
         203 . The method of  claim 200 , wherein the peptide is mixed with a pharmacologically acceptable excipient.  
     
     
         204 . The method of  claim 200 , wherein the peptide is mixed with a pharmacologically acceptable excipient suitable for oral administration to a mammal.