Duke University

Biswaranjan Pani

Robert J Lefkowitz

Laura Wingler

Seungkirl Ahn

Dean Staus

Alem W Kahsai

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.

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Durham, NC, United States of America

Biswaranjan Pani