Methods and compositions for modulating G-alpha-Q signaling
AssigneeThe University of North Carolina at Chapel Hill
InventorsJohn Sondek, Thomas Kendall Harden, Gary Lynn Waldo, Matthew Owen Barrett, Thomas Henry Charpentier
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Abstract
The present invention provides compositions and methods for modulating G-alpha-q activity and methods of screening of test substances for the ability to modulate G-alpha-q activity.
Claims17
A method of downregulating G-alpha-Q signaling in a cell, comprising introducing into the cell a peptide comprising the amino acid sequence HQDYAEALANPIKHVSL-Nle-DQR (SEQ ID NO:1).
A method of treating a cancer associated with a Gαq mutation in a subject in need thereof, comprising introducing to the subject an effective amount of a peptide comprising the amino acid sequence HQDYAEALANPIKHVSL-Nle-DQR (SEQ ID NO:1).
A method of identifying a test substance having the ability to inhibit G-alpha-q activity, comprising:
- a) contacting a peptide comprising the amino acid sequence HQDYAEALANPIKHVSL-Nle-DQRARQLAA (SEQ ID NO:
- 4) and further comprising a TAMRA label with G-alpha-q and GDP and aluminum fluoride and determining a baseline fluorescence polarization value;
- and;
- b) contacting the peptide of (a) with G-alpha-q and GDP, aluminum fluoride and the test substance and determining a fluorescence polarization value,
- wherein a fluorescence polarization value of (b) that is lower than the fluorescence polarization value of (a) identifies the test substance as having the ability to inhibit G-alpha-q activity.
A method of identifying a test substance having the ability to increase G-alpha-q activity, comprising:
- a) contacting a peptide comprising the amino acid sequence HQDYAEALANPIKHVSL-Nle-DQRARQLAA (SEQ ID NO:4) and further comprising a TAMRA label with G-alpha-q and GDP and aluminum fluoride and determining a baseline fluorescence polarization value;
- and
- b) contacting the peptide of (a) with G-alpha-q, GDP, aluminum fluoride and the test substance and determining a fluorescence polarization value,
- wherein a fluorescence polarization value of (b) that is greater than the fluorescence polarization value of (a) identifies the test substance as having the ability to increase G-alpha-q activity.
Dependencies are inferred from the claim text.