Pharmaceutical compositions and methods targeting Wnt pathway proteins
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 of enhancing a Wnt signaling pathway, comprising contacting an LRP/6 receptor in the Wnt signaling pathway with a synthetic peptide less than 50 amino acids in length, the peptide comprising a sequence of human sclerostin (SEQ ID NO: 30) that includes ELGEYPEPPPELENNK (SEQ ID NO: 5) or ELGEYPEPPPELE (SEQ ID NO: 9).
2. The method of claim 1 , wherein the synthetic peptide comprises a sequence of human sclerostin (SEQ ID NO: 30) that includes ELGEYPEPPPELENNK (SEQ ID NO: 5).
3. The method of claim 1 , wherein the synthetic peptide comprises a sequence of human sclerostin (SEQ ID NO: 30) that is ELGEYPEPPPELENNK (SEQ ID NO: 5).
4. The method of claim 1 , wherein the synthetic peptide comprises a sequence of human sclerostin (SEQ ID NO: 30) that includes ELGEYPEPPPELE (SEQ ID NO: 9).
5. A method of inhibiting binding of a protein ligand comprising a sulfation site to a binding partner, comprising
adding a synthetic peptide less than 50 amino acids in length, the peptide comprising a sequence of human sclerostin (SEQ ID NO: 30), that includes ELGEYPEPPPELENNK (SEQ ID NO: 5) or ELGEYPEPPPELE (SEQ ID NO: 9), in a manner sufficient to inhibit binding of the protein ligand to the binding partner.
6. The method of claim 5 , wherein the synthetic peptide comprises a sequence of human sclerostin (SEQ ID NO: 30) that includes ELGEYPEPPPELENNK (SEQ ID NO: 5).
7. The method of claim 5 , wherein the synthetic peptide comprises a sequence of human sclerostin that is ELGEYPEPPPELENNK (SEQ ID NO: 5).
8. The method of claim 5 , wherein the synthetic peptide comprises a sequence of human sclerostin (SEQ ID NO: 30) that includes ELGEYPEPPPELE (SEQ ID NO: 9).
9. The method of claim 1 , wherein the synthetic peptide is less than 20 amino acids in length.
10. The method of claim 5 , wherein the synthetic peptide is less than 20 amino acids in length.