Methods for treating bone loss using sclerostin peptides
Provided is a composition comprising a peptide comprising amino acids and/or amino acid analogs comprising a continuous sequence of a sclerostin fragment comprising Tyr43 or Tyr213. Also provided is a composition comprising a peptide comprising less than about 75 amino acids and/or amino acid analogs including an amino acid or amino acid analog capable of being sulfated, where the composition is capable of inhibiting sclerostin binding to an LRP. Further provided is a composition comprising a peptide comprising less than about 75 amino acids and/or amino acid analogs including an amino acid or amino acid analog capable of being post-translationally sulfated, where the composition is capable of inhibiting binding of a protein ligand comprising a sulfation site to its binding partner. Also provided are methods of using the compositions.
1. A method for treating bone loss in a human subject, comprising
administering to a human subject in need of treatment for bone loss a pharmaceutical composition comprising
a synthetic peptide less than 50 amino acids, the peptide comprising a continuous sequence of human sclerostin (SEQ ID NO:30) that includes ELGEYPEPPPELENNK (SEQ ID NO: 5) or KANQAELENAY (SEQ ID NO: 8),
wherein the peptide inhibits human sclerostin binding to an LRP.
2. The method of claim 1 , wherein
the synthetic peptide comprises a continuous sequence of human sclerostin (SEQ ID NO:30) that includes ELGEYPEPPPELENNK (SEQ ID NO: 5).
3. The method of claim 2 , wherein tyrosine in ELGEYPEPPPELENNK (SEQ ID NO: 5) is sulfated.
4. The method of claim 3 , wherein the synthetic peptide is less than 40 amino acids.
5. The method of claim 4 , wherein the synthetic peptide is less than 30 amino acids.
6. The method of claim 5 , wherein the synthetic peptide is less than 20 amino acids.
7. The method of claim 2 , wherein tyrosine in ELGEYPEPPPELENNK (SEQ ID NO: 5) is unsulfated.
8. The method of claim 7 , wherein the synthetic peptide is less than 40 amino acids.
9. The method of claim 8 , wherein the synthetic peptide is less than 30 amino acids.
10. The method of claim 9 , wherein the synthetic peptide is less than 20 amino acids.
11. The method of claim 1 , wherein
the synthetic peptide comprises a continuous sequence of human sclerostin (SEQ ID NO:30) that includes KANQAELENAY (SEQ ID NO: 8).
12. The method of claim 11 , wherein the pharmaceutical composition further comprises a pharmaceutically acceptable excipient.
13. The method of claim 1 , wherein the pharmaceutical composition further comprises a pharmaceutically acceptable excipient.
14. The method of claim 1 , wherein:
the synthetic peptide consists essentially of a continuous sequence of human sclerostin (SEQ ID NO:30) that includes ELGEYPEPPPELENNK (SEQ ID NO: 5) or KANQAELENAY (SEQ ID NO: 8).
15. The method of claim 14 , wherein
the synthetic peptide consists essentially of a continuous sequence of human sclerostin (SEQ ID NO:30) that includes tyrosine in ELGEYPEPPPELENNK (SEQ ID NO: 5).
16. The method of claim 15 , wherein tyrosine in ELGEYPEPPPELENNK (SEQ ID NO: 5) is sulfated.
17. The method of claim 15 , wherein tyrosine in ELGEYPEPPPELENNK (SEQ ID NO: 5) is unsulfated.
18. The method of claim 17 , wherein tyrosine in KANQAELENAY (SEQ ID NO: 8) is sulfated.
19. The method of claim 18 , wherein the synthetic peptide is less than 40 amino acids.
20. The method of claim 19 , wherein the synthetic peptide is less than 30 amino acids.
21. The method of claim 20 , wherein the synthetic peptide is less than 20 amino acids.
22. The method of claim 17 , wherein tyrosine in KANQAELENAY (SEQ ID NO: 8) is unsulfated.
23. The method of claim 22 , wherein the synthetic peptide is less than 40 amino acids.
24. The method of claim 23 , wherein the synthetic peptide is less than 30 amino acids.
25. The method of claim 24 , wherein the synthetic peptide is less than 20 amino acids.
26. The method of claim 15 , wherein the pharmaceutical composition further comprises a pharmaceutically acceptable excipient.
27. The method of claim 26 , wherein the synthetic peptide consists essentially of ELGEYPEPPPELENNK (SEQ ID NO: 5).
28. The method of claim 27 , wherein the synthetic peptide is the carboxy terminal amide form of ELGEYPEPPPELENNK (SEQ ID NO: 5).
29. The method of claim 14 , wherein
the synthetic peptide consists essentially of a continuous sequence of human sclerostin (SEQ ID NO:30) that includes KANQAELENAY (SEQ ID NO: 8).
30. The method of claim 29 , wherein tyrosine in KANQAELENAY (SEQ ID NO: 8) is sulfated.
31. The method of claim 29 , wherein tyrosine in KANQAELENAY (SEQ ID NO: 8) is unsulfated.
32. The method of claim 29 , wherein the pharmaceutical composition further comprises a pharmaceutically acceptable excipient.
33. The method of claim 32 , wherein the synthetic peptide consists essentially of KANQAELENAY (SEQ ID NO: 8).
34. The method of claim 14 , wherein the pharmaceutical composition further comprises a pharmaceutically acceptable excipient.
35. The method of claim 1 , wherein the human subject has an osteolytic lesion and the bone loss is associated with the osteolytic lesion.
36. The method of claim 2 , wherein the pharmaceutical composition further comprises a pharmaceutically acceptable excipient.