Methods for inhibiting CLC-2 channel with GATX2

• US 8,324,158 B2
• Filed: 07/12/2007
• Issued: 12/04/2012
• Est. Priority Date: 07/14/2006
• Status: Expired due to Fees

• Current Assignee: Georgia Tech Research Corporation (University System of Georgia)
• Original Assignee: Georgia Tech Research Corporation (University System of Georgia)
• Inventors: Thompson, Christopher H., Kubanek, Julia, McCarty, Neal
• Primary Examiner(s): HOWARD, ZACHARY C
• Application Number:
  US12/373,556
• Publication Number:
  US 20090239800A1
• Time in Patent Office: 1,972 Days
• Field of Search: None
• US Class Current: 514/7.4
• 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 method for inhibiting activity of a ClC-2 channel in a subject comprising administering to the subject an isolated peptide having at least 95% sequence identity to SEQ ID NO:

1, wherein the variation in amino acid sequence is due to a single conservative amino acid substitution, wherein the isolated peptide reduces chloride transport through the ClC-2 channel, and wherein the subject has diarrhea-predominant inflammatory bowel syndrome or secretory diarrhea.

2. The method of claim 1, wherein the isolated peptide has an apparent dissociation constant of about 12 pM for ClC-2 at −

100 mV.

3. The method of claim 1, wherein the isolated peptide is approximately a 3.2 kDa peptide.

4. The method of claim 1, wherein the isolated peptide has a calculated pI of 4.51.

5. The method of claim 1, wherein the isolated peptide is synthetic or recombinant.

6. The method of claim 1, wherein the isolated peptide is administered in a dosage form.

7. The method of claim 1, wherein the isolated peptide is isolated from venom from Leiurus quinquestriatus hebraeus.