J-superfamily conotoxin peptides
The invention relates to relatively short peptides (termed J-Superfamily conotoxin peptides, J-conotoxins or J-conotoxin peptides herein), about 25 residues in length, which are naturally available in minute amounts in the venom of the cone snails or analogous to the naturally available peptides, and which preferably include two disulfide bonds. The J-conotoxins are useful for treating disorders involving voltage gated ion channels and/or receptors.
1. An isolated modified J-conotoxin peptide selected from the group consisting of a peptide having the amino acid sequence set forth in SEQ ID NO:2, a peptide having the amino acid sequence set forth in SEQ ID NO:3, a peptide having the amino acid sequence set forth in acid SEQ ID NO:4, a peptide having the amino acid sequence set forth in SEQ ID NO:5, a peptide having the amino acid sequence set forth in SEQ ID NO:6, a peptide having the amino acid sequence set forth in SEQ ID NO:7, a peptide having the amino acid sequence set forth in SEQ ID NO:10, a peptide having the amino acid sequence set forth in SEQ ID NO:11, a peptide having the amino acid sequence set forth in SEQ ID NO:12, a peptide having the amino acid sequence set forth in SEQ ID NO:13, a peptide having the amino acid sequence set forth in SEQ ID NO:14 and a peptide having the amino acid sequence set forth in SEQ ID NO:15, wherein the peptide is modified to contain an O-glycan, an S-glycan or an N-glycan.
2. A pharmaceutical composition comprising a J-conotoxin peptide selected from the group consisting of a peptide having the amino acid sequence set forth in SEQ ID NO:2, a peptide having the amino acid sequence set forth in SEQ ID NO:3, a peptide having the amino acid sequence set forth in SEQ ID NO:4, a peptide having the amino acid sequence set forth in SEQ ID NO:5, a peptide having the amino acid sequence set forth in SEQ ID NO:6, a peptide having the amino acid sequence set forth in SEQ ID NO:7, a peptide having the amino acid sequence set forth in SEQ ID NO:10, a peptide having the amino acid sequence set forth in SEQ ID NO:11, a peptide having the amino acid sequence set forth in SEQ ID NO:12, a peptide having the amino acid sequence set forth in SEQ ID NO:13, a peptide having the amino acid sequence set forth in SEQ ID NO:14 and a peptide having the amino acid sequence set forth in SEQ ID NO:15 or a pharmaceutically acceptable salt or solvate thereof and a pharmaceutically acceptable carrier wherein the peptide is modified to contain an O-glycan, an S-glycan or an N-glycan.
3. A method of selecting for a compound that mimics the therapeutic activity of a J-conotoxin peptide, comprising the steps of: (a) conducting a biological assay on a test compound to determine the therapeutic activity; (b) conducting the same biological assay on a J-conotoxin peptide; and (c) selecting a test compound that has the same assay results as the J-conotoxin peptide as a compound that mimics the therapeutic activity of a J-conotoxin peptide, wherein the J-conotoxin peptide is selected from the group consisting of a peptide having the amino acid sequence set forth in SEQ NO:2, a peptide having the amino acid sequence set forth in SEQ ID NO:3, a peptide having the amino acid sequence set forth in SEQ ID NO:4, a peptide having the amino acid sequence set forth in SEQ ID NO:5, a peptide having the amino acid sequence set forth in SEQ ID NO:6, a peptide having the amino acid sequence set forth in SEQ ID NO:7, a peptide having the amino acid sequence set forth in SEQ ID NO:10, a peptide having the amino acid sequence set forth in SEQ ID NO:11, a peptide having the amino acid sequence set forth in SEQ ID NO:12, a peptide having the amino acid sequence set forth in SEQ ID NO:13, a peptide having the amino acid sequence set forth in SEQ ID NO:14 and a peptide having the amino acid sequence set forth in SEQ ID NO:15 of claim 1 .
4. The pharmaceutical composition of claim 3 , wherein the peptide is a peptide having the amino acid sequence set forth in SEQ ID NO:2.
5. The pharmaceutical composition of claim 3 , wherein the peptide is a peptide having the amino acid sequence set forth in SEQ ED NO:3.
6. The pharmaceutical composition of claim 3 , wherein the peptide is a peptide having the amino acid sequence set forth in SEQ ID NO:4.
7. The pharmaceutical composition of claim 3 , wherein the peptide is a peptide having the amino acid sequence set forth in SEQ ID NO:5.
8. The pharmaceutical composition of claim 3 , wherein the peptide is a peptide having the amino acid sequence set forth in SEQ ID NO:6.
9. The pharmaceutical composition of claim 3 , wherein the peptide is a peptide having the amino acid sequence set forth in SEQ ID NO:7.
10. The pharmaceutical composition of claim 3 , wherein the peptide is a peptide having the amino acid sequence set forth in SEQ ID NO:10.
11. The pharmaceutical composition of claim 3 , wherein the peptide is a peptide having the amino acid sequence set forth in SEQ ID NO:11.
12. The pharmaceutical composition of claim 3 , wherein the peptide is a peptide having the amino acid sequence set forth in SEQ ID NO:12.
13. The pharmaceutical composition of claim 3 , wherein the peptide is a peptide having the amino acid sequence set forth in SEQ ID NO:13.
14. The pharmaceutical composition of claim 3 , wherein the peptide is a peptide having the amino acid sequence set forth in SEQ ID NO:14.
15. The pharmaceutical composition of claim 3 , wherein the peptide is a peptide having the amino acid sequence set forth in SEQ ID NO:15.