ABC TRANSPORTER LIGAND

• US 20090203598A1
• Filed: 05/18/2007
• Published: 08/13/2009
• Est. Priority Date: 05/19/2006
• Status: Active Grant

• Current Assignee: Georgia Tech Research Corporation (University System of Georgia)
• Original Assignee: Georgia Tech Research Corporation (University System of Georgia)
• Inventors: Fuller, Matthew, McCarty, Nael, Kubanek, Julia
• Granted Patent: US 8,106,013 B2
• Time in Patent Office: Days
• US Class Current: 514/1.100
• CPC Class Codes: A61P 1/12 Antidiarrhoeals
• CPC Class Codes: A61P 13/12 of the kidneys
• CPC Class Codes: C07K 14/43522 from scorpions
• CPC Class Codes: Y10S 530/855 Proteins from animals other than mammals or birds

Abstract

Compositions and methods of using scorpion venom peptide that is a ligand for ABC transporters. One aspect provides a peptide having at least 80% sequence identity to SEQ ID NO: 1. The peptide Is believed to have a molecular mass of about 3.7 kDa and specifically interacts with cystic fibrosis transmembrane conductance regulator. Methods of treating a disorder or symptom of a disorder related to aberrant ABC transporter activity are also provided.

Claims

1. An isolated polypeptide comprising an amino acid sequence having at least 85% sequence identity to SEQ ID NO:

1, a variant, derivative, or prodrug thereof.

2. The isolated polypeptide of claim 1, wherein the isolated peptide is a ABC transporter ligand.

3. The isolated polypeptide of claim 2, wherein the ABC transporter is cystic fibrosis transmembrane conductance regulator.

4. The isolated polypeptide of claim 3, wherein the peptide interacts with cystic fibrosis transmembrane conductance regulator in the interburst state.

5. The isolated polypeptide of claim 4, wherein the peptide binds to the cystic fibrosis transmembrane conductance regulator.

6. The isolated polypeptide of claim 5, wherein binding of the peptide to the cystic fibrosis transmembrane conductance regulator locks closed the cystic fibrosis transmembrane conductance regulator.

10. A nucleic acid encoding the polypeptide of claim 1.

11. A method of reducing chloride transport through a chloride channel comprising contacting the chloride channel with the polypeptide of claim 1.

12. The method of claim 11, wherein the contacting occurs ex vivo.

13. The method of claim 12, wherein the chloride channel is cystic fibrosis transmembrane conductance regulator.

14. A method for treating a disorder or symptom of a disorder related to aberrant ABC transporter activity comprising:

administering a therapeutically effective amount of the polypeptide according to claim 1.

15. The method of claim 14, wherein the disorder is selected from the group consisting of cancer, cystic fibrosis, epilepsy, renal tubular disorders, Bartter'"'"'s syndrome, Dent'"'"'s disease, myotonia, osteopetrosis, Angleman or Prader-Willi, upregulation of chloride channels in glioma cells, diarrhea-predominant inflammatory bowel syndrome, autosomal dominant polycystic kidney disease (ADPKD), and secretory diarrhea.

16. An antibody that specifically binds to the polypeptide according to claim 1.

17. The antibody of claim 16, wherein the antibody is monoclonal, polyclonal, or an antigen-binding fragment thereof.

18. A pharmaceutical composition comprising an effective amount of the polypeptide according to claim 1 to reduce chloride transport through a chloride channel and a pharmaceutically acceptable diluent, preservative, solubilizer, emulsifier, adjuvant and/or carrier.

19. The pharmaceutical composition of claim 18, wherein the chloride channel is cystic fibrosis transmembrane conductance regulator.

20. Use of the polypeptide of claim 1 for the manufacture of a medicament for the treatment of aberrant ABC Transporter activity.

7. An isolated peptide ligand obtained from scorpion venom, wherein the isolated peptide ligand specifically interacts with a chloride channel.

8. The isolated peptide ligand of claim 7 wherein the peptide ligand has at least 85% sequence identity to SEQ ID NO:

1.

9. The isolated peptide ligand of claim 7 wherein the peptide ligand is obtained from Leiurus quinquestriatus hebraeus.