Peptide-based inhibitors of MLL/SET1 family core complexes
Provided are peptides, compositions comprising the peptides, and methods of using the peptide compositions for inhibition of growth of cancer cells. The peptides comprise a sequence of ARX 1 X 2 X 3 X 4 , and inhibit or disrupt the formation of MLL1 and SET1 complexes.
1. A peptide that inhibits the formation of or disrupts MLL1 and SET1 complexes, wherein the peptide is 6-50 amino acid long and comprises the following sequence: ARX 1 X 2 X 3 X 4 (SEQ ID NO:1), wherein X 1 is A, S, L, V, W, Y, or T; X 2 is E or Q; X 3 is V, P, or G; and X 4 is Y, K, or R, and wherein the N-terminus of the peptide is acetylated or the C-terminus is amidated.
2. The peptide of claim 1 , wherein ARX 1 X 2 X 3 X 4 (SEQ ID NO:1) has the following sequence: ARTEVY (SEQ ID NO:8) or ARTEPY (SEQ ID NO:9).
3. The peptide of claim 1 , wherein the peptide is 6 amino acid long.
4. The peptide of claim 1 , wherein the N-terminus of the peptide is acetylated and the C-terminus is amidated.
5. The peptide of claim 3 , wherein the N-terminus of the peptide is acetylated and the C-terminus is amidated.
6. The peptide of claim 1 , wherein the peptide is intramolecularly stapled.
7. A composition comprising a peptide of claim 1 and a pharmaceutically acceptable carrier.
8. The composition of claim 7 , wherein the peptide is 6 amino acids long.
9. The composition of claim 7 , wherein ARX 1 X 2 X 3 X 4 (SEQ ID NO: 1) is ARTEVY (SEQ ID NO:8) or ARTEPY (SEQ ID NO:9).
10. A method of inhibiting the growth of cancer cells comprising administering to an individual in need of treatment a composition of claim 7 wherein the administration results in reducing the growth of cancer cells.
11. The method of claim 10 , wherein the peptide of the composition is 6 amino acids long.
12. The method of claim 10 , wherein ARX 1 X 2 X 3 X 4 (SEQ ID NO: 1) is ARTEVY (SEQ ID NO:8) or ARTEPY (SEQ ID NO:9).
13. The method of claim 10 , wherein cancer is infant acute lymphocyctic leukemia, de novo acute myeloid leukemia, or a solid tumor.
14. The method of claim 10 , wherein the administration is combined with chemotherapy, radiation therapy, surgical removal of tumors, or combinations thereof.
15. The composition of claim 7 , wherein the N-terminus of the peptide is acetylated and the C-terminus is amidated.
16. The method of claim 10 , wherein the N-terminus of the peptide is acetylated and the C-terminus is amidated.