Tight junction protein modulators and uses thereof

1. A method for modulating apoptosis of epithelial cells of a subject comprising administering to the subject a therapeutically effective amount of a tight junction protein modulator of the formula:

wherein

each of X 1 and X 4 is independently cysteine, glutamic acid, aspartic acid, lysine, or ornithine;

each of L 1 and L 4 is independently the corresponding functional group of the amino acid side chain of X 1 and X 4 , respectively, or —(CH 2 ) m —;

each of X 2 and X 3 is glycine;

m is an integer from 1 to 4;

each n is independently 0, 1 or 2;

Z 1 is aspartic acid, glutamic acid, asparagine, or glutamine;

Z 2 is phenylalanine, tyrosine, tryptophan, or leucine;

Z 3 is tyrosine, phenylalanine, tryptophan, or leucine;

Z 4 is asparagine or glutamine; and

Z 5 is proline.

2. The method of claim 1 , wherein D is aspartic acid, F is phenylalanine, Y is tyrosine, and N is asparagine.

3. The method of claim 1 , wherein X 1 and X 4 are cysteine.

4. The method of claim 3 , wherein L 1 and L 2 together is a moiety of the formula —S—S—.

5. A method for removing at least a portion of epithelia cells from a subject, said method comprising administering to the subject in need of such treatment a tight junction protein inhibitor, wherein the epithelia cells are in hyperplastic stages, and

wherein the tight junction protein inhibitor is of the formula:

wherein

each of X 1 and X 4 is independently cysteine, glutamic acid, aspartic acid, lysine, or ornithine;

each of L 1 and L 4 is independently the corresponding functional group of the amino acid side chain of X 1 and X 4 , respectively, or —(CH 2 ) m —;

each of X 2 and X 3 is glycine;

m is an integer from 1 to 4;

each n is independently 0, 1 or 2;

Z 1 is aspartic acid, glutamic acid, asparagine, or glutamine;

Z 2 is phenylalanine, tyrosine, tryptophan, or leucine;

Z 3 is tyrosine, phenylalanine, tryptophan, or leucine;

Z 4 is asparagine or glutamine; and

Z 5 is proline.

6. The method of claim 5 , wherein the epithelia cells are in the subject's breast.

7. The method of claim 6 , wherein the tight junction protein is administered to the subject by intraductal injection.

8. A cyclic peptide of the formula:

wherein

each of X 1 and X 4 is independently cysteine, glutamic acid, aspartic acid, lysine, or ornithine;

each of L 1 and L 4 is independently the corresponding functional group of the amino acid side chain of X 1 and X 4 , respectively, or —(CH 2 ) m —;

each of X 2 and X 3 is glycine;

m is an integer from 1 to 4;

each n is independently 0, 1 or 2;

Z 1 is aspartic acid, glutamic acid, asparagine, or glutamine;

Z 2 is phenylalanine, tyrosine, tryptophan, or leucine;

Z 3 is tyrosine, phenylalanine, tryptophan, or leucine;

Z 4 is asparagine or glutamine; and

Z 5 is proline.

9. The cyclic peptide of claim 8 , wherein L 1 and L 2 together form a moiety of the formula —S—S—.