Process for identifying modulators of G-protein-coupled receptors
View Patent ↗The invention relates to a widely applicable process for identifying chemical compounds, which modulate G-protein-coupled receptors, by means of novel hybrid G-proteins with broad receptor specificity and very high expression and also to chemical compounds which can be identified by such a process.
1. A process for identifying a chemical compound modifying the action of at least one G-protein-coupled receptor (GPCR)-dependent signal transduction pathway of an organism, wherein said process comprises the following steps:
a) providing at least one cell which contains at least one GPCR-dependent signal transduction pathway and which produces one or more than one myristoylated −6q G protein hybrid;
b) providing at least one chemical compound to be studied;
c) contacting the cell of a) with one or more of the chemical compounds of b);
d) determining the quantitative or qualitative effect of the chemical compound or compounds of b) on the signal transduction pathway of the cell of a) by means of a signal transduction pathway-dependent measurable signal.
2. The process as claimed in claim 1 , wherein the cell provided according to a) produces at least two G-proteins.
3. The process as claimed in claim 1 , wherein the cell provided according to a) produces at least one protein having an amino acid sequence selected from SEQ ID NO:2 and SEQ ID NO:4.
4. The process as claimed in claim 3 , wherein the intracellular Ca 2+ concentration is the signal transduction pathway-dependent measurable signal.
5. The process as claimed in claim 4 , wherein the process is used for identifying a pharmaceutical.
6. The process as claimed in claim 3 , wherein the process is used for identifying a pharmaceutical.
7. The process as claimed in claim 1 , wherein the cell provided according to a) is the cell of a vertebrate species, an insect species, a yeast species, or a C. elegans.
8. The process as claimed in claim 7 , wherein the cell provided is a HeLa, 293, COS or CHO cell, or a cell of Saccharomyces cerevisiae.
9. The process as claimed in claim 8 , wherein the intracellular Ca 2+ concentration is the signal transduction pathway-dependent measurable signal.
10. The process as claimed in claim 9 , wherein the process is used for identifying a pharmaceutical.
11. The process as claimed in claim 8 , wherein the process is used for identifying a pharmaceutical.
12. The process as claimed in claim 7 , wherein the intracellular Ca 2+ concentration is the signal transduction pathway-dependent measurable signal.
13. The process as claimed in claim 12 , wherein the process is used for identifying a pharmaceutical.
14. The process as claimed in claim 7 , wherein the process is used for identifying a pharmaceutical.
15. The process as claimed in claim 1 , wherein the intracellular Ca 2+ concentration is the signal transduction pathway-dependent measurable signal.
16. The process as claimed in claim 15 , wherein the process is used for identifying a pharmaceutical.
17. The process as claimed in claim 1 , wherein the process is used for identifying a pharmaceutical.
18. The process as claimed in claim 2 , wherein the cell provided according to a) produces at least one protein having an amino acid sequence selected from SEQ ID NO:2 and SEQ ID NO:4.
19. The process as claimed in claim 18 , wherein the intracellular Ca 2+ concentration is the signal transduction pathway-dependent measurable signal.
20. The process as claimed in claim 19 , wherein the process is used for identifying a pharmaceutical.
21. The process as claimed in claim 18 , wherein the process is used for identifying a pharmaceutical.
22. The process is claimed in claim 2 , wherein the intracellular Ca 2+ concentration is the signal transduction pathway-dependent measurable signal.
23. The process as claimed in claim 22 , wherein the process is used for identifying a pharmaceutical.
24. The process as claimed in claim 2 , wherein the process is used for identifying a pharmaceutical.
25. The process as claimed in claim 1 or claim 2 , wherein the cell provided according to a) produces the myristoylated −6q G protein hybrid wherein said hybrid is selected from the group consisting of −6qi4myr and −6qs5myr.
26. The process as claimed in claim 25 , wherein the cell provided according to a) produces at least one protein having an amino acid sequence selected from SEQ ID NO:2 and SEQ ID NO:4.
27. The process as claimed in claim 26 , wherein the intracellular Ca 2+ concentration is the signal transduction pathway-dependent measurable signal.
28. The process as claimed in claim 27 , wherein the process is used for identifying a pharmaceutical.
29. The process as claimed in claim 26 , wherein the process is used for identifying a pharmaceutical.
30. The process as claimed in claim 25 , wherein the intracellular Ca 2+ concentration is the signal transduction pathway-dependent measurable signal.
31. The process as claimed in claim 30 , wherein the process is used for identifying a pharmaceutical.
32. The process as claimed in claim 25 , wherein the process is used for identifying a pharmaceutical.
33. The process as claimed in claim 1 or claim 2 , wherein the cell provided according to a) further produces a Gα16 G protein.
34. The process as claimed in claim 33 , wherein the intracellular Ca 2+ concentration is the signal transduction pathway-dependent measurable signal.
35. The process as claimed in claim 34 , wherein the process is used for identifying a pharmaceutical.
36. The process as claimed in claim 33 , wherein the process is used for identifying a pharmaceutical.