Inhibition of gliadin peptides

Abstract

Novel compounds and methods for the inhibition of biological barrier permeability and for the inhibition of peptide translocation across biological barriers are identified. Assays for determining modulators of biological barrier permeability and for peptide translocation across biological barriers are provided. Methods for treating diseases relating to aberrant biological barrier permeability and peptide translocation across biological barriers are provided. Such diseases include celiac disease, necrotizing enterocolitis, diabetes, cancer, inflammatory bowel diseases, asthma, COPD, excessive or undesirable immune response, gluten sensitivity, gluten allergy, food allergy, rheumatoid arthritis, multiple sclerosis, immune-mediated or type 1 diabetes mellitus, systemic lupus erythematosus, psoriasis, scleroderma and autoimmune thyroid diseases.

1 . A peptide permeability inhibitor consisting of an amino acid sequence selected from the group consisting of SEQ ID NOs: 1-162, wherein said peptide permeability inhibitor inhibits translocation of a gliadin-derived peptide across a biological barrier. 
     
     
         2 . The peptide of  claim 1 , wherein the peptide does not consist of an amino acid sequence selected from the group consisting of SEQ ID NOs: 15, 24 and 25. 
     
     
         3 . The peptide of  claim 1 , wherein the peptide consists of an amino acid sequence selected from the group consisting of SEQ ID NOs: 1-5, 10-17, 19-23, 27, 32, 34, 36, 48, 49, 55, 58, 67-77, 79-85, 87, 88, 91, 92, 94, 98-104, 106, 110, 111, 113-125, 127, 128, 147, 150, and 160-162. 
     
     
         4 . A method of inhibiting gliadin-derived peptide translocation across a biological barrier comprising contacting said barrier with a peptide permeability inhibitor consisting of an amino acid sequence selected from the group consisting of SEQ ID NOs: 1-162. 
     
     
         5 . The method of  claim 4 , wherein the peptide does not consist of an amino acid sequence selected from the group consisting of SEQ ID NOs: 15, 24 and 25. 
     
     
         6 . The method of  claim 4 , wherein the peptide consists of an amino acid sequence selected from the group consisting of SEQ ID NOs: 1-5, 10-17, 19-23, 27, 32, 34, 36, 48, 49, 55, 58, 67-77, 79-85, 87, 88, 91, 92, 94, 98-104, 106, 110, 111, 113-125, 127, 128, 147, 150, and 160-162. 
     
     
         7 . A composition for inhibiting gliadin-derived peptide translocation across a biological barrier, wherein said composition comprises a peptide permeability inhibitor consisting of an amino acid sequence selected from the group consisting of SEQ ID NOs: 1-162. 
     
     
         8 - 9 . (canceled) 
     
     
         10 . A method for inhibiting gliadin-derived peptide translocation across a biological barrier comprising administering to a subject in need thereof the composition of  claim 7  in an amount sufficient to inhibit said gliadin-derived peptide translocation. 
     
     
         11 - 30 . (canceled) 
     
     
         31 . A method of treating a patient with celiac disease, comprising administering to the patient a composition comprising a peptide that inhibits translocation of a gliadin-derived peptide across a biological barrier. 
     
     
         32 . The method of  claim 31 , wherein said composition comprises peptide consisting of an amino acid sequence selected from the group consisting of SEQ ID NOs: 1-162. 
     
     
         33 . The method of  claim 32 , wherein the peptide does not consist of an amino acid sequence selected from the group consisting of SEQ ID NOs: 15, 24 and 25. 
     
     
         34 . The method of  claim 32 , wherein the peptide consists of an amino acid sequence selected from the group consisting of SEQ ID NOs: 1-5, 10-17, 19-23, 27, 32, 34, 36, 48, 49, 55, 58, 67-77, 79-85, 87, 88, 91, 92, 94, 98-104, 106, 110, 111, 113-125, 127, 128, 147, 150, and 160-162. 
     
     
         35 . The method of  claim 31 , wherein said composition further comprises an additional therapeutic agent selected from the group consisting of aminosalicylates, corticosteroids, immunomodulators, antibiotics, cytokines, chemokines and biologic therapeutics. 
     
     
         36 - 45 . (canceled)