Dean Patrick Staus

US Patent:

20190241642, Aug 8, 2019

Filed:

Feb 7, 2019

Appl. No.:

16/269877

Inventors:

- Durham NC, US
Seungkirl Ahn - Durham NC, US
Biswaranjan Pani - Durham NC, US
Alem W. Kahsai - Durham NC, US
Laura Wingler - Durham NC, US
Dean Staus - Durham NC, US

International Classification:

C07K 14/705
C07K 14/47
G01N 33/68

Abstract:

The disclosure is directed to a G-protein coupled receptor complex. The complex includes (i) a chimeric G protein-coupled receptor (GPCR) comprising a non-native amino acid sequence located within the C-terminus of the GPCR and a synthetic phosphopeptide ligated to the non-native amino acid sequence; and (ii) a β-arrestin (βarr) protein bound to the C-terminus of the GPCR. The disclosure also provides an in vitro method for producing the aforementioned complex, as well as methods for identifying compounds or ligands which bind to and modulate the activity of the complex. Positive allosteric modulators of the β2 adrenergic receptor identified by screening a DNA-encoded library potentiate the activity of β2 agonists and have application in the treatment of obstructive airway disease, bronchospasm, or pre-term labor.