ABC transporter ligand GATX1

• US 8,106,013 B2
• Filed: 05/18/2007
• Issued: 01/31/2012
• Est. Priority Date: 05/19/2006
• 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: McCarty, Nael, Fuller, Matthew, Kubanek, Julia
• Primary Examiner(s): Bunner, Bridget E
• Assistant Examiner(s): Howard, Zachary
• Application Number:
  US12/299,881
• Publication Number:
  US 20090203598A1
• Time in Patent Office: 1,719 Days
• Field of Search: None
• US Class Current: 514/17.4
• 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 514/867 Diarrhea
• 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. A single polypeptide isolated from scorpion L. quinquestriatus hebraeus venom comprising the amino acid sequence of SEQ ID NO:

1.

2. The polypeptide of claim 1, wherein the polypeptide binds cystic fibrosis transmembrane conductance regulator.

3. The polypeptide of claim 2, wherein the polypeptide interacts with cystic fibrosis transmembrane conductance regulator in the interburst state.

4. The polypeptide of claim 3, wherein binding of the polypeptide to the cystic fibrosis transmembrane conductance regulator locks closed the cystic fibrosis transmembrane conductance regulator.

6. A pharmaceutical composition comprising an effective amount of the polypeptide according to claim 1 or 5 to reduce chloride transport through cystic fibrosis transmembrane conductance regulator and a pharmaceutically acceptable diluent, preservative, solubilizer, emulsifier, adjuvant or carrier.

7. A composition comprising the polypeptide of claim 1 or 5.

8. An ex vivo method of reducing chloride transport through a cystic fibrosis transmembrane conductance regulator (CFTR) channel comprising contacting the CFTR channel with the polypeptide of claim 1 or 5.

9. A method for treating a disorder or symptom of a disorder related to increased cystic fibrosis transmembrane conductance regulator (CFTR) activity comprising:

administering a therapeutically effective amount of the polypeptide according to claim 1 or 5, wherein the disorder is diarrhea-predominant inflammatory bowel syndrome, autosomal dominant polycystic kidney disease (ADPKD), or secretory diarrhea.

10. An in vivo method of reducing chloride transport through cystic fibrosis transmembrane conductance regulator (CFTR) in a subject having a disorder related to increased CFTR activity, comprising administering to the polypeptide of claim 1 or 5 such that CFTR is contacted with the polypeptide, wherein the disorder is diarrhea-predominant inflammatory bowel syndrome, autosomal dominant polycystic kidney disease (ADPKD), or secretory diarrhea.

5. An isolated synthetic or recombinant polypeptide comprising the amino acid sequence of SEQ ID NO:

1.