Method for Preventing and Treating Hyperpermeability

Abstract

A peptide is described, which consists of 7-17 adjacent amino acids and comprises the hexamer TX EX X E, wherein X, X and X can be any natural or non-natural amino acid, wherein the peptide has no TNF receptor binding activity and is cyclized, for the prevention and treatment of hyperpermeability of epithelial cells and endothelial cells.

1 . A peptide consisting of 7-17 adjacent amino acids and comprising the hexamer TX EX X E, wherein X, X and X can be any natural or non-natural amino acid, wherein the peptide has no TNF receptor binding activity and is cyclized, for the prevention and treatment of hyperpermeability of epithelial cells and endothelial cells. 
     
     
         2 . The peptide consisting of 7-17 adjacent amino acids and comprising the hexamer TPEGAE, wherein the peptide has no TNF receptor binding activity and is cyclized, for the prevention and treatment of hyperpermeability of epithelial cells and endothelial cells. 
     
     
         3 . A cyclized peptide consisting of a sequence of consecutive amino acids selected from the group consisting of 
       
         
           
                 
                 
               
                     
                   QRETPEGAEAKPWY; 
                 
                     
                     
                 
                     
                   PKDTPEGAELKPWY; 
                 
                     
                     
                 
                     
                   CGQRETPEGAEAKPWYC; 
                 
                     
                   and 
                 
                     
                     
                 
                     
                   CGPKDTPEGAELKPWYC; 
                 
             
                
                
                
                
                
                
                
                
               
            
           
         
       
       and fragments of at least 7 amino acids thereof, which fragments include the hexamer TPEGAE, for manufacturing a drug for preventing and treating hyperpermeability of epithelial cells and endothelial cells. 
     
     
         4 . The peptide according to  claim 1 , for treating pneumonia, acute lung injury, acute respiratory distress syndrome (ADRS) or bacterial or viral lung diseases, in particular infections with  Listeria monocytogenes, Streptococcus pneumoniae,  SARS viruses, RSV or influenza viruses. 
     
     
         5 . The peptide according to  claim 1 , characterized in that it comprises the amino acid sequence CGQRETPEGAEAKPWYC and is cyclized via the C residues. 
     
     
         6 . The peptide according to  claim 5 , characterized in that it is cyclized via a disulfide bridge between said C residues. 
     
     
         7 . The peptide according to  claim 1 , characterized in that it is used for protecting epithelial cells and endothelial cells against hyperpermeability triggered by reactive oxygen molecules. 
     
     
         8 . The peptide according to  claim 1 , characterized in that it is used for protecting epithelial cells and endothelial cells against hyperpermeability triggered by bacterial toxins. 
     
     
         9 . The peptide according to  claim 1 , characterized in that it is used for inhibiting the phosphorylation of the myosin light chain. 
     
     
         10 . The peptide according to  claim 1 , characterized in that it is used for inhibiting the activation of protein kinase C. 
     
     
         11 . The peptide according to  claim 1 , characterized in that it is used for increasing the expression of the epithelial sodium channel. 
     
     
         12 . The peptide according to  claim 1 , characterized in that it is used for treating hyperpermeability triggered by reactive oxygen molecules, microbial toxins, gram-positive microorganisms or pulmonary virus infections. 
     
     
         13 . A pharmaceutical composition comprising a peptide according to  claim 1 .