Anti-angiogenic peptides for treating or preventing endometriosis
Provided herein are peptides from the N-terminal of endostatin proteins, including the first histidine of the protein, nucleic acids encoding the peptides, pharmaceutical compositions comprising the nucleic acids and proteins and methods for using the pharmaceutical compositions to treat or prevent endometriosis in a subject.
1. A method for treating endometriosis in a subject comprising administering to a subject in need thereof a therapeutically effective amount of a peptide, consisting of 10 to 35 amino acids of the N-terminal region of a human endostatin protein including the first histidine of the endostatin protein, or variant thereof, wherein the peptide does not consist of SEQ ID NO: 48.
2. The method of claim 1 , wherein the peptide consists of 21 to 30 amino acids.
3. The method of claim 1 , wherein the peptide is selected from the group consisting of SEQ ID NOs: 2, 6, 38, 40, 42, 44, 46, 50, 52, 54, 56, 58, 60, 62, 64, 125, 126, 130, and 131.
4. The method of claim 1 , wherein the peptide contains a substitution, deletion or addition of one amino acid relative to the naturally occurring sequence.
5. The method of claim 1 , wherein the peptide contains a substitution, deletion or addition of two amino acids relative to the naturally occurring sequence.
6. The method of claim 1 , wherein the peptide contains a deletion or addition of three amino acids relative to the naturally occurring sequence.
7. The method of claim 1 , further comprising administering to the subject an effective amount of zinc.
8. The method of claim 1 , further comprising administering to the subject a second peptide.
9. The method of claim 1 , wherein the peptide is SEQ ID NO: 2.
10. The method of claim 1 , wherein the peptide consists of 10 to 35 amino acids of the N-terminal region of a human endostatin protein including the first histidine of the endostatin protein, wherein the peptide does not consist of SEQ TD NO: 48.
11. The method of claim 1 , wherein the peptide consists of 12 amino acids of SEQ ID NO: 2 or 6 including the first histidine.
12. The method of claim 1 , wherein the peptide is SEQ ID NO: 6.
13. The method of claim 1 , wherein the peptide consists of an amino acid sequence that is at least 95% identical to SEQ ID NO: 2, 6, 38, 40, 42, 44, 46, 50, 52, 54, 56, 58, 60, 62, 64, 125 or 126.
14. The method of claim 1 , wherein the peptide is linked to a heterologous peptide.
15. The method of claim 3 , wherein the peptide is linked to a heterologous peptide.
16. The method of claim 13 , wherein the peptide is linked to a heterologous peptide.
17. A method for treating endometriosis in a subject comprising administering to a subject in need thereof a therapeutically effective amount of a peptide, consisting of 10 to 35 amino acids of the N-terminal region of an endostatin protein including the first histidine of the endostatin protein, or variant thereof, wherein the peptide does not consist of SEQ ID NO: 48, 102 or 108.
18. The method of claim 17 , wherein the peptide consists of 10 to 35 amino acids of the N-terminal region of an endostatin protein including the first histidine of the endostatin protein.
19. The method of claim 17 , wherein the peptide consists of 21 to 30 amino acids.
20. The method of claim 17 , wherein the peptide consists of an amino acid sequence that is at least 95% identical to SEQ ID NO: 4, 96, 98, 100, 104, 106, 110, 112, 114, 116, 118, 120, 122, 124, 128 or 129.
21. The method of claim 20 , wherein the peptide is selected from the group consisting of SEQ ID NOs: 4, 96, 98, 100, 104, 106, 110, 112, 114, 116, 118, 120, 122, 124, 128 and 129.
22. The method of claim 21 , wherein the peptide consists of SEQ ID NO: 4.
23. The method of claim 20 , wherein the peptide consists of 12 amino acids of SEQ ID NO: 4.
24. The method of claim 17 , wherein the peptide is linked to a heterologous peptide.
25. The method of claim 20 , wherein the peptide is linked to a heterologous peptide.
26. The method of claim 21 , wherein the peptide is linked to a heterologous peptide.
27. The method of claim 1 , wherein the subject is human.
28. The method of claim 3 , wherein the subject is human.
29. The method of claim 13 , wherein the subject is human.
30. The method of claim 17 , wherein the subject is human.
31. The method of claim 20 , wherein the subject is human.
32. The method of claim 21 , wherein the subject is human.