Peptides Having Immunomodulatory Properties

Abstract

The present disclosure provides novel peptides that having immunomodulatory activities in vitro and in vivo. The peptides can include a particular striapathic region of alternating hydrophilic and hydrophobic modules that can adopt an amphipathic conformation under physiological conditions. This disclosure provides peptides that can specifically bind to key functional regions on one or more signaling proteins, particularly pro-inflammatory cytokines, macrophage inhibition proteins, and histone regulation proteins. This disclosure includes peptides that are sufficiently stable in the circulation to allow for intravenous administration. Pharmaceutical compositions including the subject peptides are also provided. The subject peptides find use in methods of modulating macrophage activity. In some cases, the peptide is a CD206-binding agent. Also provided are methods of treating a subject for a condition associated with chronic inflammation using the peptides and compositions of this disclosure.

What is claimed is: 
     
         1 . An immunomodulatory peptide, comprising:
 a) a peptide sequence selected from SEQ ID NO: (1-19); or   b) a sequence having one or two amino acid substitutions relative to the sequence defined in a), wherein the one or two amino acid substitutions are substitutions for amino acids according to Table 2.   
     
     
         2 . The immunomodulatory peptide of  claim 1 , wherein the one or two amino acid substitutions defined in b) consist of a highly conservative substitution of a cationic amino acid of the sequence. 
     
     
         3 . The immunomodulatory peptide of  claim 1 , comprising the peptide sequence selected from: 
       
         
           
                 
                 
               
                     
                   (SEQ ID NO: 1) 
                 
                     
                   RWKFGGFKWR (RP832C), 
                 
                     
                   (SEQ ID NO: 3) 
                 
                     
                   FKWRGGRWKF (RP837C) and 
                 
                     
                   (SEQ ID NO: 4) 
                 
                     
                   FWKRGGRKWF (RP837A). 
                 
             
                
                
                
                
                
                
               
            
           
         
       
     
     
         4 . The immunomodulatory peptide of  claim 3 , comprising the peptide sequence selected from 
       
         
           
                 
                 
               
                     
                   (SEQ ID NO: 5) 
                 
                     
                   FWKRFV (RP837N) and 
                 
                     
                   (SEQ ID NO: 16) 
                 
                     
                   FVRKWR (RP837C). 
                 
             
                
                
                
                
               
            
           
         
       
     
     
         5 . The immunomodulatory peptide of  claim 1 , comprising a peptide sequence selected from 
       
         
           
                 
                 
               
                     
                   (SEQ ID NO: 19) 
                 
                     
                   FAOOFAOOFO (RP850), 
                 
                     
                   (SEQ ID NO: 2) 
                 
                     
                   FWKRFVRKWR (RP837) and 
                 
                     
                   (SEQ ID NO: 7) 
                 
                     
                   FWKKFVKKWK (RP841).  
                 
             
                
                
                
                
                
                
               
            
           
         
       
     
     
         6 . The immunomodulatory peptide of  claim 1 , comprising a peptide sequence selected from 
       
         
           
                 
                 
               
                     
                   (SEQ ID NO: 13) 
                 
                     
                   WWHHWWHHWH, 
                 
                     
                   (SEQ ID NO: 14) 
                 
                     
                   WWRHWWHRWR and 
                 
                     
                   (SEQ ID NO: 15) 
                 
                     
                   WWKHWWHKWK (RP847-849).   
                 
             
                
                
                
                
                
                
               
            
           
         
       
     
     
         7 . The immunomodulatory peptide of  claim 1 , comprising the peptide sequence GDRGIKGHRGF (RP842) (SEQ ID NO: 8). 
     
     
         8 . The immunomodulatory peptide of  claim 1 , comprising the peptide sequence LYKKIIKKLL (RP846) (SEQ ID NO: 12). 
     
     
         9 . The immunomodulatory peptide of  claim 1 , comprising the peptide sequence FYPDFFKKFF (RP844) (SEQ ID NO: 10). 
     
     
         10 . The immunomodulatory peptide of  claim 1 , comprising the peptide sequence FFRKSKEKIG (RP853) (SEQ ID NO: 18). 
     
     
         11 . The immunomodulatory peptide of  claim 1 , comprising the peptide sequence FFRHFATHLD (RP845) (SEQ ID NO: 11). 
     
     
         12 . The immunomodulatory peptide of  claim 1 , comprising the peptide sequence EKLSAFRNFF (RP843) (SEQ ID NO: 9). 
     
     
         13 . A pharmaceutical composition, comprising the immunomodulatory peptide of  claim 1  and a pharmaceutically acceptable carrier. 
     
     
         14 . A peptide of 12 amino acid residues or less in length, comprising a sequence selected from: 
       
         
           
                 
                 
               
                     
                   (SEQ ID NO: 1) 
                 
                     
                   RWKFGGFKWR (RP832C), 
                 
                     
                   (SEQ ID NO: 3) 
                 
                     
                   FKWRGGRWKF (RP837C) and 
                 
                     
                   (SEQ ID NO: 4) 
                 
                     
                   FWKRGGRKWF (RP837A). 
                 
             
                
                
                
                
                
                
               
            
           
         
       
     
     
         15 . The peptide of  claim 14 , comprising the sequence: RWKFGGFKWR (RP832C) (SEQ ID NO: 1). 
     
     
         16 . The peptide of  claim 14 , comprising the sequence: FKWRGGRWKF (RP837C) (SEQ ID NO: 3). 
     
     
         17 . The peptide of  claim 14 , comprising the sequence: FWKRGGRKWF (RP837A) (SEQ ID NO: 4). 
     
     
         18 . A method of treating a subject for a condition associated with chronic inflammation, the method comprising:
 administering an effective amount of a peptide according to  claim 1  to the subject to treat the subject for the condition associated with chronic inflammation.   
     
     
         19 . The method according to  claim 18 , wherein the condition associated with chronic inflammation is selected from the group consisting of scleroderma or multiple sclerosis, irritable bowel disease, ulcerative colitis, colitis, Crohn's disease, idiopathic pulmonary fibrosis, scleroderma, asthma, keratitis, arthritis, osteoarthritis, rheumatoid arthritis, auto-immune diseases, a feline or human immunodeficiency virus (FIV or HIV) infection, cancer, age-related inflammation and/or stem cell dysfunction, graft-versus-host disease (GVHD), keloids, obesity, diabetes, diabetic wounds, other chronic wounds, atherosclerosis, Parkinson's disease, Alzheimer's disease, macular degeneration, gout, gastric ulcers, gastritis, mucositis, toxoplasmosis, and chronic viral or microbial infections. 
     
     
         20 . The method according to  claim 19 , wherein the condition is cancer. 
     
     
         21 . The method according to  claim 20 , further comprising administering an effective amount of a chemotherapeutic agent or an immunotherapeutic agent to the subject. 
     
     
         22 . The method according to  claim 18 , wherein the condition associated with chronic inflammation is a fibrosis. 
     
     
         23 . The method according to  claim 18 , wherein the condition associated with chronic inflammation is scleroderma.