Methods of identifying and ADP-glucose receptor ligand, agonist or antagonist

• US 6,790,608 B2
• Filed: 02/09/2001
• Issued: 09/14/2004
• Est. Priority Date: 09/20/2000
• Status: Expired due to Term

• Current Assignee: Regents of the University of California (University of California)
• Original Assignee: Regents of the University of California (University of California)
• Inventors: Wang, Zhiwei, Civelli, Olivier, Reinscheid, Rainer, Nothacker, Hans-Peter
• Primary Examiner(s): Kunz, Gary
• Assistant Examiner(s): Li, Ruixiang
• Application Number:
  US09/780,576
• Publication Number:
  US 20020072072A1
• Time in Patent Office: 1,313 Days
• Field of Search: 435/4, 435/7.1, 436/66, 530/350
• US Class Current: 435/4
• CPC Class Codes: G01N 33/66 involving blood sugars, e.g. galactose

Abstract

The present invention provides an isolated nucleic acid molecule containing a nucleotide sequence which encodes an ADP-glucose receptor, and isolated polynucleotides therefrom. Also provided is an isolated ADP-glucose receptor polypeptide, an isolated immunogenic peptide therefrom, and antibodies specific therefor. The invention also provides a method of identifying an ADP-glucose receptor agonist or antagonist, by contacting an ADP-glucose receptor with one or more candidate compounds under conditions suitable for detection of a G-protein coupled signal in response to ADP-glucose, and identifying a candidate compound that alters production of the signal. Further provided is a method of identifying an ADP-glucose receptor ligand, by contacting an ADP-glucose receptor with one or more candidate compounds under conditions suitable for detecting selective binding of ADP-glucose to ADP-glucose receptor, and identifying a candidate compound that selectively binds the ADP-glucose receptor. Also provided are methods of diagnosing or determining susceptibility to ADP-glucose receptor associated conditions, by detecting in a sample from the individual expression of ADP glucose receptor nucleic acid molecules or polypeptides.

Claims

1. A method of identifying an ADP-glucose receptor agonist or antagonist, comprising:

(a) contacting an ADP-glucose receptor polypeptide with at least one candidate compound in the presence of ADP-glucose under conditions wherein said receptor produces a G-protein coupled signal in response to ADP-glucose, wherein said ADP-glucose receptor polypeptide has the amino acid sequence designated SEQ ID NO;

2;

(b) determining the ability of said candidate compound to alter production of said G-protein coupled signal, wherein a candidate compound that alters production of said signal is identified as an ADP-glucose receptor agonist or antagonist.

2. The method of claim 1, wherein said G-protein coupled signal is increased intracellular calcium ion concentration.

3. The method of claim 1, wherein said receptor is contacted with 2 or more different candidate compounds.

4. The method of claim 1, wherein said receptor is contacted with a library of candidate compounds.

5. The method of claim 1, wherein said receptor is contacted with 100 or more different compounds separately.

6. A method of identifying an ADP-glucose receptor agonist, comprising:

(a) contacting an ADP-glucose receptor polypeptide with at least one candidate compound under conditions that permit said receptor to produce a G-protein coupled signal in response to ADP-glucose, wherein said ADP-glucose receptor polypeptide has the amino acid sequence designated SEQ ID NO;

2; and

(b) determining the ability of said candidate compound to increase production of said G-protein coupled signal, wherein a candidate compound that increases production of said signal is thereby identified as an ADP-glucose receptor agonist.

7. The method of claim 6, wherein said G-protein coupled signal is increased intracellular calcium ion concentration.

8. The method of claim 6, wherein said receptor is contacted with 2 or more different candidate compounds.

9. The method of claim 6, wherein said candidate compound contacts said ADP-glucose receptor polypeptide in the presence of ADP-glucose.

10. The method of claim 6, wherein said receptor is contacted with a library of candidate compounds.

11. The method of claim 6, wherein said receptor is contacted with 100 or more different compounds separately.

12. A method of identifying an ADP-glucose receptor ligand, comprising:

(a) contacting an ADP-glucose receptor polypeptide with at least one candidate compound under conditions that permit said receptor to selectively bind ADP-glucose, wherein said ADP-glucose receptor polypeptide has the amino acid sequence designated SEQ ID NO;

2; and

(b) determining the ability of said candidate compound to bind said ADP glucose receptor, wherein a candidate compound that selectively binds said ADP-glucose receptor is thereby identified as an ADP-glucose receptor ligand.

13. The method of claim 12, wherein said receptor is contacted with 2 or more different candidate compounds.

14. The method of claim 12, wherein said candidate compound contacts said ADP-glucose receptor polypeptide in the presence of ADP-glucose.

15. The method of claim 12, wherein said receptor is contacted with a library of candidate compounds.

16. The method of claim 12, wherein said receptor is contacted with 100 or more different compounds separately.

17. A method of identifying an ADP-glucose receptor ligand, comprising:

(a) contacting an ADP-glucose receptor polypeptide with at least one candidate compound in the presence of ADP-glucose under conditions that permit said receptor to selectively bind ADP-glucose, wherein said ADP-glucose receptor polypeptide has the amino acid sequence designated SEQ ID NO;

2; and

(b) determining the ability of said candidate compound to bind said ADP-glucose receptor, wherein a candidate compound that selectively binds said ADP-glucose receptor is thereby identified as an ADP-glucose receptor ligand.

18. The method of claim 17, wherein maid receptor is contacted with 2 or more different candidate compounds.

19. The method of claim 17, wherein said receptor is contacted with a library of candidate compounds.

20. The method of claim 17, wherein said receptor is contacted with 100 or more different compounds separately.