Inhibition of gliadin peptides
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 inhibitor of tight junction permeability comprising an amino acid sequence selected from: Gly- D -Pro- D -Gln- D -Val- D -Leu- D -Val-Gly-Gly (SEQ ID NO: 81), Gly- D -Pro- D -Gln- D -Val- D -Leu-Val-Gly-Gly (SEQ ID NO: 82), Gly- D -Pro- D -Gln- D -Val-Leu- D -Val-Gly-Gly (SEQ ID NO: 83), Gly- D -Pro- D -Gln-Val- D -Leu- D -Val-Gly-Gly (SEQ ID NO: 84), Gly- D -Pro-Gln- D -Val- D -Leu- D -Val-Gly-Gly (SEQ ID NO: 85), Gly-Pro-Gln-Val-Leu-Val-Gly-Gly (SEQ ID NO: 87), Gly- D -Pro-Gln-Val-Leu-Val-Gly-Gly (SEQ ID NO: 88), Gly-Pro-Gln-Val- D -Leu-Val-Gly-Gly (SEQ ID NO: 91), and Gly-Pro-Gln-Val-Leu- D -Val-Gly-Gly (SEQ ID NO: 92).
2. A composition comprising the peptide of claim 1 formulated for pulmonary delivery.
3. A composition comprising the peptide of claim 1 formulated for intestinal delivery.
4. The composition of claim 2 , wherein the peptide is an amino acid sequence having the sequence of Gly- D -Pro- D -Gln- D -Val- D -Leu- D -Val-Gly-Gly (SEQ ID NO: 81).
5. The composition of claim 2 , wherein the peptide is an amino acid sequence having the sequence of Gly- D -Pro- D -Gln- D -Val- D -Leu-Val-Gly-Gly (SEQ ID NO: 82).
6. The composition of claim 2 , wherein the peptide is an amino acid sequence having the sequence of Gly- D -Pro- D -Gln- D -Val-Leu- D -Val-Gly-Gly (SEQ ID NO: 83).
7. The composition of claim 2 , wherein the peptide is an amino acid sequence having the sequence of Gly- D -Pro- D -Gln-Val- D -Leu- D -Val-Gly-Gly (SEQ ID NO: 84).
8. The composition of claim 2 , wherein the peptide is an amino acid sequence having the sequence of Gly- D -Pro-Gln- D -Val- D -Leu- D -Val-Gly-Gly (SEQ ID NO: 85).
9. The composition of claim 2 , wherein the peptide is an amino acid sequence having the sequence of Gly-Pro-Gln-Val-Leu-Val-Gly-Gly (SEQ ID NO: 87).
10. The composition of claim 2 , wherein the peptide is an amino acid sequence having the sequence of Gly- D -Pro-Gln-Val-Leu-Val-Gly-Gly (SEQ ID NO: 88).
11. The composition of claim 2 , wherein the peptide is an amino acid sequence having the sequence of Gly-Pro-Gln-Val- D -Leu-Val-Gly-Gly (SEQ ID NO: 91).
12. The composition of claim 2 , wherein the peptide is an amino acid sequence having the sequence of Gly-Pro-Gln-Val-Leu- D -Val-Gly-Gly (SEQ ID NO: 92).
13. The composition of claim 2 , further comprising an additional therapeutic agent selected from aminosalicylates, corticosteroids, immunomodulators, antibiotics, cytokines, chemokines and biologic therapeutics.
14. The composition of claim 3 , further comprising an additional therapeutic agent selected from aminosalicylates, corticosteroids, immunomodulators, antibiotics, cytokines, chemokines and biologic therapeutics.