Novel peptides that enhance tight junction permeability

Abstract

The present invention provides novel peptides that facilitate the opening of mammalian tight junctions, i.e. tight junction agonists. The present invention also provides methods for the treatment of disease by administering to a subject suffering from the disease a composition comprising a peptide tight junction agonist of the invention in combination with a therapeutically effective amount of an active agent.

1 . A peptide tight junction agonist comprising the amino acid sequence of SEQ ID NO:1, with at least one amino acid substitution, deletion, or insertion, or at least one chemical modification, with respect to SEQ ID NO: 1. 
     
     
         2 .- 4 . (canceled) 
     
     
         5 . The tight junction agonist of  claim 1 , wherein the position corresponding to position 2 of SEQ ID NO: 1 is AllylGly. 
     
     
         6 .- 9 . (canceled) 
     
     
         10 . The tight junction agonist of  claim 1 , wherein the tight junction agonist has a terminal basic group after the position corresponding to position 5 or 6 of SEQ ID NO: 1. 
     
     
         11 . The tight junction agonist of  claim 10 , wherein the basic functional group is an amine. 
     
     
         12 . The tight junction agonist of  claim 1  comprising a substitution of at least one non-genetically encoded amino acid. 
     
     
         13 .- 14 . (canceled) 
     
     
         15 . The tight junction agonist of  claim 1 , wherein the agonist is from 3 to 10 amino acids in length. 
     
     
         16 .- 17 . (canceled) 
     
     
         18 . The peptide tight junction agonist of  claim 1 , wherein the peptide comprises an amino acid sequence selected from the group of SEQ ID NOs: 2-90. 
     
     
         19 .- 25 . (canceled) 
     
     
         26 . The peptide tight junction agonist of  claim 1 , wherein the peptide comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 73-90. 
     
     
         27 . The peptide tight junction agonist of  claim 26 , wherein the peptide comprises an amino acid sequence selected from the group consisting of SEQ ID NOs:73, 74, 76, 85, and 88. 
     
     
         28 . (canceled) 
     
     
         29 . A composition comprising the peptide tight junction agonist of  claim 1 . 
     
     
         30 .- 34 . (canceled) 
     
     
         35 . A pharmaceutical composition comprising the peptide tight junction agonist of  claim 1  and at least one pharmaceutically acceptable excipient. 
     
     
         36 .- 40 . (canceled) 
     
     
         41 . A method of treating a disease in a subject in need thereof, comprising: administering to the subject an effective dose of the peptide tight junction agonist of  claim 1 . 
     
     
         42 . A method of treating a disease in a subject in need thereof, comprising: administering to the subject an effective dose of the composition of  claim 29 . 
     
     
         43 . A method of treating a disease in a subject in need thereof, comprising: administering to the subject an effective dose of the pharmaceutical composition of  claim 35 . 
     
     
         44 .- 48 . (canceled)