Neuropeptide Q as modulator of GPCR GALR2 and uses thereof
AssigneeActelion Pharmaceuticals Ltd.
InventorXavier Leroy
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Abstract
The invention relates to the identification of Neuropeptide Q as ligand of the GALR2 GPCR (G-protein coupled receptor). The invention encompasses the use of the interaction of GALR2 polypeptides and Neuropeptide Q polypeptides as the basis of screening assays for agents that modulate the activity of the GALR2 receptor. The invention also encompasses diagnostic assays based upon the GALR2/Neuropeptide Q polypeptide interaction, as well as kits for performing diagnostic and screening assays.
Claims19
A method of identifying an agent that modulates the function of GALR2 comprising:
- a) contacting a GALR2 polypeptide with a Neuropeptide Q polypeptide in the presence and absence of a candidate modulator under conditions permitting the interaction of the Neuropeptide Q polypeptide to the GALR2 polypeptide, wherein the candidate modulator is a synthetic compound;
- and
- b) measuring the interaction of the GALR2 polypeptide to the Neuropeptide Q polypeptide, wherein an increase or a decrease in interaction in the presence of the candidate modulator, relative to the interaction in the absence of the candidate modulator, identifies the candidate modulator as an agent that modulates the function of GALR2,
- wherein the GALR2 polypeptide is a polypeptide having at least 95% amino acid sequence identity to SEQ ID NO:
- 2, 4, 6, 8, or 10, and
- wherein the Neuropeptide Q polypeptide is a polypeptide having at least 90% amino acid sequence identity to SEQ ID NO:
- 13-16 or 18-41.
A method of identifying an agent that modulates the function of GALR2 comprising:
- a) contacting a GALR2 polypeptide with a Neuropeptide Q polypeptide in the presence and absence of a candidate modulator under conditions permitting the interaction of the Neuropeptide Q polypeptide to the GALR2 polypeptide, wherein the candidate modulator is a synthetic compound;
- and
- b) measuring a signaling activity of the GALR2 polypeptide, wherein a change in the activity in the presence of the candidate modulator relative to the activity in the absence of the candidate modulator identifies the candidate modulator as an agent that modulates the function of GALR2,
- wherein the GALR2 polypeptide is a polypeptide having at least 95% amino acid sequence identity to SEQ ID NO:
- 2, 4, 6, 8, or 10, and
- wherein the Neuropeptide Q polypeptide is a polypeptide having at least 90% amino acid sequence identity to SEQ ID NO:
- 13-16 or 18-41.
A method of identifying an agent that modulates the function of GALR2 comprising:
- a) contacting a GALR2 polypeptide with a candidate modulator, wherein the candidate modulator is a synthetic compound;
- b) measuring a signaling activity of the GALR2 polypeptide in the presence of the candidate modulator;
- and
- c) comparing the activity measured in the presence of the candidate modulator to the activity measured in a sample in which the GALR2 polypeptide is contacted with a Neuropeptide Q polypeptide,
- wherein the candidate modulator is identified as an agent that modulates the function of GALR2 when the amount of the activity measured in the presence of the candidate modulator is at least 50% of the amount induced by the Neuropeptide Q polypeptide present at its EC50,
- wherein the GALR2 polypeptide is a polypeptide having at least 95% amino acid sequence identity to SEQ ID NO:
- 2, 4, 6, 8, or 10, and
- wherein the Neuropeptide Q polypeptide is a polypeptide having at least 90% amino acid sequence identity to SEQ ID NO:
- 13-16 or 18-41.
Dependencies are inferred from the claim text.