CLC Channel Ligand

• US 20090239800A1
• Filed: 07/12/2007
• Published: 09/24/2009
• Est. Priority Date: 07/14/2006
• Status: Active Grant

• Current Assignee: Georgia Tech Research Corporation (University System of Georgia)
• Original Assignee: Georgia Tech Research Corporation (University System of Georgia)
• Inventors: Thompson, Christopher H., McCarty, Nael, Kubanek, Julia
• Granted Patent: US 8,324,158 B2
• Time in Patent Office: Days
• US Class Current: 514/1.100
• CPC Class Codes: A61K 38/1767 from invertebrates
• CPC Class Codes: A61P 1/12 Antidiarrhoeals

Abstract

Compositions and methods of using scorpion venom peptide that is a ligand for ClC channels are provided. One aspect provides a pharmaceutical composition containing an amount of GaTx2 effective to inhibit ClC activity. Methods of treating a disorder or symptom of a disorder related to aberrant ClC channel activity are also provided.

Claims

1. A pharmaceutical composition comprising an effective amount of a polypeptide having at least 97% sequence identity to SEQ ID NO:

1 to reduce chloride transport through a chloride channel and a pharmaceutically acceptable diluent, preservative, solubilizer, emulsifier, adjuvant and/or carrier.

2. The pharmaceutical composition of claim 1, wherein the chloride channel is a ClC channel.

3. The pharmaceutical composition of claim 2, wherein the chloride channel is ClC-2.

4. A method for treating aberrant ClC channel activity comprising

administering to a host or patient in need thereof a peptide having at least 97% sequence identity to SEQ ID NO:

1 to reduce chloride transport through a chloride channel.

5. The method of claim 4, wherein the chloride channel is a ClC channel.

6. The method of claim 5, wherein the chloride channel is ClC-2.

7. The method of claim 4, wherein the aberrant ClC channel activity is a result of a disease or disorder selected from the group consisting of cancer, cystic fibrosis, epilepsy, renal tubular disorders, Bartters 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), excitotoxic neuronal injury, and secretory diarrhea.

8. A method for inhibiting overactive chloride channels comprising

administering to a host or patient in need thereof an effective amount of a peptide having at least 97% sequence identity to SEQ ID NO:

1 to inhibit or reduce chloride channel activity.

9. A method for isolating ClC-2 protein comprising:

attaching a peptide having at least 97% sequence identity to SEQ ID NO;

1 to a solid support; and

contacting the peptide on the solid support with a sample comprising ClC-2 under conditions promoting the interaction of the peptide with ClC-2 to retain ClC-2.

10. The method of claim 9, further comprising washing the solid support to remove non-specifically bound components.

11. The method of claim 10, further comprising eluting ClC-2 from the solid support.

12. A method for stabilizing the conformation of ClC-2 comprising

contacting ClC-2 with an effective amount of a peptide having at least 97% sequence identity to SEQ ID NO:

1 to bind and stabilize ClC-2.

13. The method of claim 12, wherein the contacting occurs in vitro.

14. Use of a polypeptide having at least 97% sequence identity to SEQ ID NO:

1 for the manufacture of a medicament for the treatment of aberrant ClC channel activity.

15. The use of claim 14, wherein the ClC channel is ClC-2.

16. The use of claim 14, wherein the aberrant ClC channel activity is related to a disease or disorder 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), excitotoxic neuronal injury, and secretory diarrhea.