Novel inhibitors of mammalian tight junction opening

Abstract

The present invention provides novel peptides that inhibit and/or reduce the opening of mammalian tight junctions, i.e. peptide tight junction antagonists. The present invention also provides methods for the treatment of excessive or undesirable permeability of a tissue by administering to a subject suffering from such a condition a composition comprising a peptide tight junction antagonist of the invention.

What is claimed is: 
     
         1 . A peptide tight junction antagonist, wherein the peptide comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 2-69. 
     
     
         2 . The peptide tight junction antagonist of  claim 1 , wherein the peptide is eight to ten amino acids in length. 
     
     
         3 . The peptide tight junction antagonist of  claim 1 , wherein the peptide comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 3-11, 13, 17, 18, 20-32, 34, 35, 54, 57, and 67-69. 
     
     
         4 . The peptide tight junction antagonist of  claim 1 , wherein the peptide consists essentially of an amino acid sequence selected from the group consisting of SEQ ID NOs: 2-69. 
     
     
         5 . The peptide tight junction antagonist of  claim 1 , wherein the peptide consists essentially of an amino acid sequence selected from the group consisting of SEQ ID NOs: 3-11, 13, 17, 18, 20-32, 34, 35, 54, 57, and 67-69. 
     
     
         6 . The peptide tight junction antagonist of  claim 1 , wherein the peptide consists of an amino acid sequence selected from the group consisting of SEQ ID NOs: 2-69. 
     
     
         7 . The peptide tight junction antagonist of  claim 1 , wherein the peptide consists of an amino acid sequence selected from the group consisting of SEQ ID NOs: 3-11, 13, 17, 18, 20-32, 34, 35, 54, 57, and 67-69. 
     
     
         8 . A method of treating an excessive or undesirable permeability of a tissue containing tight junctions comprising:
 administering to a subject in need thereof a composition comprising a peptide tight junction antagonist, wherein the peptide comprises an amino acid sequence selected from the group of SEQ ID NOs: 2-69.   
     
     
         9 . The method of  claim 8 , wherein the subject is a human. 
     
     
         10 . The method of  claim 8 , wherein the peptide is eight to ten amino acids in length. 
     
     
         11 . The method of  claim 8 , wherein the peptide comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 3-11, 13, 17, 18, 20-32, 34, 35, 54, 57, and 67-69. 
     
     
         12 . The method of  claim 8 , wherein the peptide consists essentially of an amino acid sequence selected from the group of SEQ ID NOs: 2-69. 
     
     
         13 . The method of  claim 8 , wherein the peptide consists essentially of an amino acid sequence selected from the group consisting of SEQ ID NOs: 3-11, 13, 17, 18, 20-32, 34, 35, 54, 57, and 67-69. 
     
     
         14 . The method of  claim 8 , wherein the peptide consists of an amino acid sequence selected from the group of SEQ ID NOs: 2-69. 
     
     
         15 . The method of  claim 8 , wherein the peptide consists of an amino acid sequence selected from the group consisting of SEQ ID NOs: 3-11, 13, 17, 18, 20-32, 34, 35, 54, 57, and 67-69. 
     
     
         16 . The method of  claim 8 , wherein the composition further comprises an additional therapeutic agent. 
     
     
         17 . The method of  claim 16 , wherein the additional therapeutic agent is selected from the group consisting of aminosalicylates, corticosteroids, immunomodulators, antibiotics, cytokines, chemokines and biologic therapeutics. 
     
     
         18 . The method of  claim 8 , wherein the composition is formulated for intestinal delivery. 
     
     
         19 . The method of  claim 8 , wherein the composition is formulated for pulmonary delivery. 
     
     
         20 . The method of  claim 8  wherein said excessive or undesirable permeability of a tissue containing tight junctions is associated with a disease selected form the group consisting of celiac disease; inflammatory bowel disease; Crohn's disease; ulcerative colitis; acute respiratory distress syndrome; acute lung injury; chronic obstructive pulmonary disorder; type 1 diabetes; and asthma. 
     
     
         21 . A method of treating inflammatory bowel disease comprising:
 administering to a subject in need thereof a composition comprising a peptide tight junction antagonist, wherein the peptide comprises an amino acid sequence selected from the group of SEQ ID NOs: 2-69.   
     
     
         22 . The method of  claim 21 , wherein the subject is a human. 
     
     
         23 . The method of  claim 21 , wherein the peptide is eight to ten amino acids in length. 
     
     
         24 . The method of  claim 21 , wherein the peptide comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 3-11, 13, 17, 18, 20-32, 34, 35, 54, 57, and 67-69. 
     
     
         25 . The method of  claim 21 , wherein the peptide consists essentially of an amino acid sequence selected from the group of SEQ ID NOs: 2-69. 
     
     
         26 . The method of  claim 21 , wherein the peptide consists essentially of an amino acid sequence selected from the group consisting of SEQ ID NOs: 3-11, 13, 17, 18, 20-32, 34, 35, 54, 57, and 67-69. 
     
     
         27 . The method of  claim 21 , wherein the peptide consists of an amino acid sequence selected from the group of SEQ ID NOs: 2-69. 
     
     
         28 . The method of  claim 21 , wherein the peptide consists of an amino acid sequence selected from the group consisting of SEQ ID NOs: 3-11, 13, 17, 18, 20-32, 34, 35, 54, 57, and 67-69. 
     
     
         29 . The method of  claim 21 , wherein the composition further comprises an additional therapeutic agent. 
     
     
         30 . The method of  claim 29 , wherein the additional therapeutic agent is selected from the group consisting of aminosalicylates, corticosteroids, immunomodulators, antibiotics, cytokines, chemokines and biologic therapeutics. 
     
     
         31 . The method of  claim 21 , wherein the composition is formulated for intestinal delivery. 
     
     
         32 . A method of treating Crohn's disease comprising:
 administering to a subject in need thereof a composition comprising a peptide tight junction antagonist, wherein the peptide comprises an amino acid sequence selected from the group of SEQ ID NOs: 2-69.   
     
     
         33 . The method of  claim 32 , wherein the subject is a human. 
     
     
         34 . The method of  claim 32 , wherein the peptide is eight to ten amino acids in length. 
     
     
         35 . The method of  claim 32 , wherein the peptide comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 3-11, 13, 17, 18, 20-32, 34, 35, 54, 57, and 67-69. 
     
     
         36 . The method of  claim 32 , wherein the peptide consists essentially of an amino acid sequence selected from the group of SEQ ID NOs: 2-69. 
     
     
         37 . The method of  claim 32 , wherein the peptide consists essentially of an amino acid sequence selected from the group consisting of SEQ ID NOs: 3-11, 13, 17, 18, 20-32, 34, 35, 54, 57, and 67-69. 
     
     
         38 . The method of  claim 32 , wherein the peptide consists of an amino acid sequence selected from the group of SEQ ID NOs: 2-69. 
     
     
         39 . The method of  claim 32 , wherein the peptide consists of an amino acid sequence selected from the group consisting of SEQ ID NOs: 3-11, 13, 17, 18, 20-32, 34, 35, 54, 57, and 67-69. 
     
     
         40 . The method of  claim 32 , wherein the composition further comprises an additional therapeutic agent. 
     
     
         41 . The method of  claim 40 , wherein the additional therapeutic agent is selected from the group consisting of aminosalicylates, corticosteroids, immunomodulators, antibiotics, cytokines, chemokines and biologic therapeutics. 
     
     
         42 . The method of  claim 32 , wherein the composition is formulated for intestinal delivery. 
     
     
         43 . A method of treating ulcerative colitis comprising:
 administering to a subject in need thereof a composition comprising a peptide tight junction antagonist, wherein the peptide comprises an amino acid sequence selected from the group of SEQ ID NOs: 2-69.   
     
     
         44 . The method of  claim 43 , wherein the subject is a human. 
     
     
         45 . The method of  claim 43 , wherein the peptide is eight to ten amino acids in length. 
     
     
         46 . The method of  claim 43 , wherein the peptide comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 3-11, 13, 17, 18, 20-32, 34, 35, 54, 57, and 67-69. 
     
     
         47 . The method of  claim 43 , wherein the peptide consists essentially of an amino acid sequence selected from the group of SEQ ID NOs: 2-69. 
     
     
         48 . The method of  claim 43 , wherein the peptide consists essentially of an amino acid sequence selected from the group consisting of SEQ ID NOs: 3-11, 13, 17, 18, 20-32, 34, 35, 54, 57, and 67-69. 
     
     
         49 . The method of  claim 43 , wherein the peptide consists of an amino acid sequence selected from the group of SEQ ID NOs: 2-69. 
     
     
         50 . The method of  claim 43 , wherein the peptide consists of an amino acid sequence selected from the group consisting of SEQ ID NOs: 3-11, 13, 17, 18, 20-32, 34, 35, 54, 57, and 67-69 
     
     
         51 . The method of  claim 43 , wherein the composition further comprises a therapeutic agent. 
     
     
         52 . The method of  claim 51 , wherein the therapeutic agent is selected from the group consisting of amino salicylates, corticosteroids, immunomodulators, antibiotics, cytokines, chemokines and biologic therapeutics. 
     
     
         53 . The method of  claim 43 , wherein the composition is formulated for intestinal delivery. 
     
     
         54 . A method of treating Celiac disease comprising:
 administering to a subject in need thereof a composition comprising a peptide tight junction antagonist, wherein the peptide comprises an amino acid sequence selected from the group of SEQ ID NOs: 2-69.   
     
     
         55 . The method of  claim 54 , wherein the subject is a human. 
     
     
         56 . The method of  claim 54 , wherein the peptide is eight to ten amino acids in length. 
     
     
         57 . The method of  claim 54 , wherein the peptide comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 3-11, 13, 17, 18, 20-32, 34, 35, 54, 57, and 67-69. 
     
     
         58 . The method of  claim 54 , wherein the peptide consists essentially of an amino acid sequence selected from the group of SEQ ID NOs: 2-69. 
     
     
         59 . The method of  claim 54 , wherein the peptide consists essentially of an amino acid sequence selected from the group consisting of SEQ ID NOs: 3-11, 13, 17, 18, 20-32, 34, 35, 54, 57, and 67-69. 
     
     
         60 . The method of  claim 54 , wherein the peptide consists of an amino acid sequence selected from the group of SEQ ID NOs: 2-69. 
     
     
         61 . The method of  claim 54 , wherein the peptide consists of an amino acid sequence selected from the group consisting of SEQ ID NOs: 3-11, 13, 17, 18, 20-32, 34, 35, 54, 57, and 67-69. 
     
     
         62 . The method of  claim 54 , wherein the composition is formulated for intestinal delivery. 
     
     
         63 . A method of treating acute respiratory distress syndrome comprising:
 administering to a subject in need thereof a composition comprising a peptide tight junction antagonist, wherein the peptide comprises an amino acid sequence selected from the group of SEQ ID NOs: 2-69.   
     
     
         64 . The method of  claim 63 , wherein the subject is a human. 
     
     
         65 . The method of  claim 63 , wherein the peptide is eight to ten amino acids in length. 
     
     
         66 . The method of  claim 63 , wherein the peptide comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 3-11, 13, 17, 18, 20-32, 34, 35, 54, 57, and 67-69. 
     
     
         67 . The method of  claim 63 , wherein the peptide consists essentially of an amino acid sequence selected from the group of SEQ ID NOs: 2-69. 
     
     
         68 . The method of  claim 63 , wherein the peptide consists essentially of an amino acid sequence selected from the group consisting of SEQ ID NOs: 3-11, 13, 17, 18, 20-32, 34, 35, 54, 57, and 67-69. 
     
     
         69 . The method of  claim 63 , wherein the peptide consists of an amino acid sequence selected from the group of SEQ ID NOs: 2-69. 
     
     
         70 . The method of  claim 63 , wherein the peptide consists of an amino acid sequence selected from the group consisting of SEQ ID NOs: 3-11, 13, 17, 18, 20-32, 34, 35, 54, 57, and 67-69. 
     
     
         71 . The method of  claim 63 , wherein the composition is formulated for pulmonary delivery. 
     
     
         72 . A method of treating acute lung injury comprising:
 administering to a subject in need thereof a composition comprising a peptide tight junction antagonist, wherein the peptide comprises an amino acid sequence selected from the group of SEQ ID NOs: 2-69.   
     
     
         73 . The method of  claim 72 , wherein the subject is a human. 
     
     
         74 . The method of  claim 72 , wherein the peptide is eight to ten amino acids in length. 
     
     
         75 . The method of  claim 72 , wherein the peptide comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 3-11, 13, 17, 18, 20-32, 34, 35, 54, 57, and 67-69. 
     
     
         76 . The method of  claim 72 , wherein the peptide consists essentially of an amino acid sequence selected from the group of SEQ ID NOs: 2-69. 
     
     
         77 . The method of  claim 72 , wherein the peptide consists essentially of an amino acid sequence selected from the group consisting of SEQ ID NOs: 3-11, 13, 17, 18, 20-32, 34, 35, 54, 57, and 67-69. 
     
     
         78 . The method of  claim 72 , wherein the peptide consists of an amino acid sequence selected from the group of SEQ ID NOs: 2-69. 
     
     
         79 . The method of  claim 72 , wherein the peptide consists of an amino acid sequence selected from the group consisting of SEQ ID NOs: 3-11, 13, 17, 18, 20-32, 34, 35, 54, 57, and 67-69. 
     
     
         80 . The method of  claim 72 , wherein the composition is formulated for pulmonary delivery. 
     
     
         81 . A method of treating chronic obstructive pulmonary disorder comprising:
 administering to a subject in need thereof a composition comprising a peptide tight junction antagonist, wherein the peptide comprises an amino acid sequence selected from the group of SEQ ID NOs: 2-69.   
     
     
         82 . The method of  claim 81 , wherein the subject is a human. 
     
     
         83 . The method of  claim 81 , wherein the peptide is eight to ten amino acids in length. 
     
     
         84 . The method of  claim 81 , wherein the peptide comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 3-11, 13, 17, 18, 20-32, 34, 35, 54, 57, and 67-69. 
     
     
         85 . The method of  claim 81 , wherein the peptide consists essentially of an amino acid sequence selected from the group of SEQ ID NOs: 2-69. 
     
     
         86 . The method of  claim 81 , wherein the peptide consists essentially of an amino acid sequence selected from the group consisting of SEQ ID NOs: 3-11, 13, 17, 18, 20-32, 34, 35, 54, 57, and 67-69. 
     
     
         87 . The method of  claim 81 , wherein the peptide consists of an amino acid sequence selected from the group of SEQ ID NOs: 2-69. 
     
     
         88 . The method of  claim 81 , wherein the peptide consists of an amino acid sequence selected from the group consisting of SEQ ID NOs: 3-11, 13, 17, 18, 20-32, 34, 35, 54, 57, and 67-69. 
     
     
         89 . The method of  claim 81 , wherein the composition is formulated for pulmonary delivery. 
     
     
         90 . A method of treating type 1 diabetes comprising:
 administering to a subject in need thereof a composition comprising a peptide tight junction antagonist, wherein the peptide comprises an amino acid sequence selected from the group of SEQ ID NOs: 2-69.   
     
     
         91 . The method of  claim 90 , wherein the subject is a human. 
     
     
         92 . The method of  claim 90 , wherein the peptide is eight to ten amino acids in length. 
     
     
         93 . The method of  claim 90 , wherein the peptide comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 3-11, 13, 17, 18, 20-32, 34, 35, 54, 57, and 67-69. 
     
     
         94 . The method of  claim 90 , wherein the peptide consists essentially of an amino acid sequence selected from the group of SEQ ID NOs: 2-69. 
     
     
         95 . The method of  claim 90 , wherein the peptide consists essentially of an amino acid sequence selected from the group consisting of SEQ ID NOs: 3-11, 13, 17, 18, 20-32, 34, 35, 54, 57, and 67-69. 
     
     
         96 . The method of  claim 90 , wherein the peptide consists of an amino acid sequence selected from the group of SEQ ID NOs: 2-69. 
     
     
         97 . The method of  claim 90 , wherein the peptide consists of an amino acid sequence selected from the group consisting of SEQ ID NOs: 3-11, 13, 17, 18, 20-32, 34, 35, 54, 57, and 67-69. 
     
     
         98 . The method of  claim 90 , wherein the composition is formulated for intestinal delivery. 
     
     
         99 . The method of  claim 90 , wherein the composition is formulated for pulmonary delivery. 
     
     
         100 . A method of treating asthma comprising:
 administering to a subject in need thereof a composition comprising a peptide tight junction antagonist, wherein the peptide comprises an amino acid sequence selected from the group of SEQ ID NOs: 2-69.   
     
     
         101 . The method of  claim 99 , wherein the subject is a human. 
     
     
         102 . The method of  claim 99 , wherein the peptide is eight to ten amino acids in length. 
     
     
         103 . The method of  claim 99 , wherein the peptide comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 3-11, 13, 17, 18, 20-32, 34, 35, 54, 57, and 67-69. 
     
     
         104 . The method of  claim 99 , wherein the peptide consists essentially of an amino acid sequence selected from the group of SEQ ID NOs: 2-69. 
     
     
         105 . The method of  claim 99 , wherein the peptide consists essentially of an amino acid sequence selected from the group consisting of SEQ ID NOs: 3-11, 13, 17, 18, 20-32, 34, 35, 54, 57, and 67-69. 
     
     
         106 . The method of  claim 99 , wherein the peptide consists of an amino acid sequence selected from the group of SEQ ID NOs: 2-69. 
     
     
         107 . The method of  claim 99 , wherein the peptide consists of an amino acid sequence selected from the group consisting of SEQ ID NOs: 3-11, 13, 17, 18, 20-32, 34, 35, 54, 57, and 67-69. 
     
     
         108 . The method of  claim 99 , wherein the composition is formulated for pulmonary delivery. 
     
     
         109 . The peptide tight junction antagonist of  claim 1 , wherein the peptide comprises the amino acid sequence of SEQ ID NO 3. 
     
     
         110 . The peptide tight junction antagonist of  claim 1 , wherein the peptide comprises the amino acid sequence of SEQ ID NO:4. 
     
     
         111 . The peptide tight junction antagonist of  claim 1 , wherein the peptide comprises the amino acid sequence of SEQ ID NO:5. 
     
     
         112 . The peptide tight junction antagonist of  claim 1 , wherein the peptide comprises the amino acid sequence of SEQ ID NO:6. 
     
     
         113 . The peptide tight junction antagonist of  claim 1 , wherein the peptide comprises the amino acid sequence of SEQ ID NO:7. 
     
     
         114 . The peptide tight junction antagonist of  claim 1 , wherein the peptide comprises the amino acid sequence of SEQ ID NO:8. 
     
     
         115 . The peptide tight junction antagonist of  claim 1 , wherein the peptide comprises the amino acid sequence of SEQ ID NO:9. 
     
     
         116 . The peptide tight junction antagonist of  claim 1 , wherein the peptide comprises the amino acid sequence of SEQ ID NO:10. 
     
     
         117 . The peptide tight junction antagonist of  claim 1 , wherein the peptide comprises the amino acid sequence of SEQ ID NO:11. 
     
     
         118 . The peptide tight junction antagonist of  claim 1 , wherein the peptide comprises the amino acid sequence of SEQ ID NO:13. 
     
     
         119 . The peptide tight junction antagonist of  claim 1 , wherein the peptide comprises the amino acid sequence of SEQ ID NO:17. 
     
     
         120 . The peptide tight junction antagonist of  claim 1 , wherein the peptide comprises the amino acid sequence of SEQ ID NO:18. 
     
     
         121 . The peptide tight junction antagonist of  claim 1 , wherein the peptide comprises the amino acid sequence of SEQ ID NO:20. 
     
     
         122 . The peptide tight junction antagonist of  claim 1 , wherein the peptide comprises the amino acid sequence of SEQ ID NO:21. 
     
     
         123 . The peptide tight junction antagonist of  claim 1 , wherein the peptide comprises the amino acid sequence of SEQ ID NO:22. 
     
     
         124 . The peptide tight junction antagonist of  claim 1 , wherein the peptide comprises the amino acid sequence of SEQ ID NO:23. 
     
     
         125 . The peptide tight junction antagonist of  claim 1 , wherein the peptide comprises the amino acid sequence of SEQ ID NO:24. 
     
     
         126 . The peptide tight junction antagonist of  claim 1 , wherein the peptide comprises the amino acid sequence of SEQ ID NO:25. 
     
     
         127 . The peptide tight junction antagonist of  claim 1 , wherein the peptide comprises the amino acid sequence of SEQ ID NO:26. 
     
     
         128 . The peptide tight junction antagonist of  claim 1 , wherein the peptide comprises the amino acid sequence of SEQ ID NO:27. 
     
     
         129 . The peptide tight junction antagonist of  claim 1 , wherein the peptide comprises the amino acid sequence of SEQ ID NO:28. 
     
     
         130 . The peptide tight junction antagonist of  claim 1 , wherein the peptide comprises the amino acid sequence of SEQ ID NO:29. 
     
     
         131 . The peptide tight junction antagonist of  claim 1 , wherein the peptide comprises the amino acid sequence of SEQ ID NO:30. 
     
     
         132 . The peptide tight junction antagonist of  claim 1 , wherein the peptide comprises the amino acid sequence of SEQ ID NO:31. 
     
     
         133 . The peptide tight junction antagonist of  claim 1 , wherein the peptide comprises the amino acid sequence of SEQ ID NO:32. 
     
     
         134 . The peptide tight junction antagonist of  claim 1 , wherein the peptide comprises the amino acid sequence of SEQ ID NO:34. 
     
     
         135 . The peptide tight junction antagonist of  claim 1 , wherein the peptide comprises the amino acid sequence of SEQ ID NO:35. 
     
     
         136 . The peptide tight junction antagonist of  claim 1 , wherein the peptide comprises the amino acid sequence of SEQ ID NO:54. 
     
     
         137 . The peptide tight junction antagonist of  claim 1 , wherein the peptide comprises the amino acid sequence of SEQ ID NO:57. 
     
     
         138 . The peptide tight junction antagonist of  claim 1 , wherein the peptide comprises the amino acid sequence of SEQ ID NO:67. 
     
     
         139 . The peptide tight junction antagonist of  claim 1 , wherein the peptide comprises the amino acid sequence of SEQ ID NO:68. 
     
     
         140 . The peptide tight junction antagonist of  claim 1 , wherein the peptide comprises the amino acid sequence of SEQ ID NO:69. 
     
     
         141 . A method of treating an excessive or undesirable permeability of a tissue containing tight junctions comprising:
 administering to a subject in need thereof a composition comprising the peptide tight junction antagonist of any one of  claims 109 - 140 .   
     
     
         142 . A method of treating inflammatory bowel disease comprising:
 administering to a subject in need thereof a composition comprising the peptide tight junction antagonist of any one of  claims 109 - 140 .   
     
     
         143 . A method of treating Crohn's disease comprising:
 administering to a subject in need thereof a composition comprising the peptide tight junction antagonist of any one of  claims 109 - 140 .   
     
     
         144 . A method of treating ulcerative colitis comprising:
 administering to a subject in need thereof a composition comprising the peptide tight junction antagonist of any one of  claims 109 - 140 .   
     
     
         145 . A method of treating Celiac disease comprising:
 administering to a subject in need thereof a composition comprising the peptide tight junction antagonist of any one of  claims 109 - 140 .   
     
     
         146 . A method of treating acute respiratory distress syndrome comprising:
 administering to a subject in need thereof a composition comprising the peptide tight junction antagonist of any one of  claims 109 - 140 .   
     
     
         147 . A method of treating acute lung injury comprising:
 administering to a subject in need thereof a composition comprising the peptide tight junction antagonist of any one of  claims 109 - 140 .   
     
     
         148 . A method of treating chronic obstructive pulmonary disorder comprising:
 administering to a subject in need thereof a composition comprising the peptide tight junction antagonist of any one of  claims 109 - 140 .   
     
     
         149 . A method of treating type 1 diabetes comprising:
 administering to a subject in need thereof a composition comprising the peptide tight junction antagonist of any one of  claims 109 - 140 .   
     
     
         150 . A method of treating asthma comprising:
 administering to a subject in need thereof a composition comprising the peptide tight junction antagonist of any one of  claims 109 - 140 .   
     
     
         151 . A pharmaceutical composition comprising a peptide that reduces tight junction permeability and a pharmaceutically acceptable carrier and/or excipient, the peptide having from 3 to 5 amino acids. 
     
     
         152 . The pharmaceutical composition of  claim 151 , wherein the peptide is defined by the formula: X 1 -X 2 -X 3 -X 4 -X 5 ; wherein:
 X 1  is optional, and where present is a natural or non-natural amino acid;   X 2  is optional, and where present is a natural or non-natural amino acid;   X 3  is a natural or non-natural amino acid;   X 4  is selected from Pro or Ala; and   X 5  is Gly, Gln, or Ala.   
     
     
         153 . The pharmaceutical composition of  claim 152 , wherein X 1  and X 2  are not present. 
     
     
         154 . The pharmaceutical composition of  claim 152  or  153 , wherein X 3  is a genetically-encoded amino acid. 
     
     
         155 . The pharmaceutical composition of  claim 152  or  153 , wherein X 3  is selected from Gln, (d)Gln, Ala, Gly, His, Arg, Phe, Glu, Lys, Leu, Met, Asn, Ser, Tyr, Ile, Trp, and Glp. 
     
     
         156 . The pharmaceutical composition of any one of  claims 152  to  155 , wherein X 4  is Pro. 
     
     
         157 . The pharmaceutical composition of  claim 156 , wherein X 3  is Gln. 
     
     
         158 . The pharmaceutical composition of any one of  claims 152  to  157 , wherein X 5  is Gly. 
     
     
         159 . The pharmaceutical composition of  claim 152  or  153 , wherein X 3  is Gin, X 4  is Pro, and X 5  is Gly. 
     
     
         160 . The pharmaceutical composition of any one of  claims 151  to  159 , wherein the composition is formulated for pulmonary delivery. 
     
     
         161 . The pharmaceutical composition of  claim 160 , wherein the composition is formulated as an aerosol. 
     
     
         162 . A method for reducing tight junction permeability of lung tissue, comprising, administering the pharmaceutical composition of any one of  claim 160  or  161  to a patient in need. 
     
     
         163 . The method of  claim 162 , wherein the patient is afflicted with one or more of asthma, acute respiratory distress syndrome, acute lung injury, and chronic obstructive pulmonary disorder. 
     
     
         164 . The method of  claim 162  or  163 , wherein the patient is human. 
     
     
         165 . The pharmaceutical composition of any one of  claims 151  to  159 , wherein the composition is formulated for intestinal delivery. 
     
     
         166 . A method for reducing tight junction permeability of intestinal tissue, comprising, administering the pharmaceutical composition of  claim 165  to a patient in need. 
     
     
         167 . The method of  claim 166 , wherein the patient is afflicted with one or more of celiac disease, inflammatory bowel disease, Crohn's disease, ulcerative colitis, and type 1 diabetes. 
     
     
         168 . The method of  claim 166  or  167 , wherein the patient is human.