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 ?-arrestin (?arr) 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 ?2 adrenergic receptor identified by screening a DNA-encoded library potentiate the activity of ?2 agonists and have application in the treatment of obstructive airway disease, bronchospasm, or pre-term labor.

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 ?-arrestin (?arr) 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 ?2 adrenergic receptor identified by screening a DNA-encoded library potentiate the activity of ?2 agonists and have application in the treatment of obstructive airway disease, bronchospasm, or pre-term labor.

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 ?-arrestin (?arr) 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 ?2 adrenergic receptor identified by screening a DNA-encoded library potentiate the activity of ?2 agonists and have application in the treatment of obstructive airway disease, bronchospasm, or pre-term labor.