Development and Characterization of Pepducins as Gs-biased Allosteric Agonists

• Published in: The Journal of biological chemistry Vol. 289; no. 52; pp. 35668 - 35684
• Main Authors: Carr, Richard, Du, Yang, Quoyer, Julie, Panettieri, Reynold A., Janz, Jay M., Bouvier, Michel, Kobilka, Brian K., Benovic, Jeffrey L.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 26.12.2014; American Society for Biochemistry and Molecular Biology
• Subjects: Adrenergic beta-Agonists - pharmacology; Adrenergic Receptor; Allosteric Regulation; Amino Acid Sequence; Asthma; Biased Agonist; Cyclic AMP - biosynthesis; Drug Discovery; Functional Selectivity; G Protein-coupled Receptor (GPCR); GTP-Binding Protein alpha Subunits, Gs - metabolism; HEK293 Cells; Humans; Molecular Sequence Data; Pepducin; Peptide Fragments - chemistry; Peptide Fragments - pharmacology; Peptide Library; Peptides; Phosphorylation; Protein Binding; Protein Processing, Post-Translational; Protein Structure, Tertiary; Protein Transport; Receptors, Adrenergic, beta-2 - chemistry; Receptors, Adrenergic, beta-2 - metabolism; Second Messenger Systems; Signal Transduction; β2-Adrenergic Receptor; Functional Selectivity; Peptides; Signal Transduction; Adrenergic Receptor; Pepducin; β2-Adrenergic Receptor; Biased Agonist; Drug Discovery; G Protein-coupled Receptor (GPCR); Asthma

The β2-adrenergic receptor (β2AR) is a prototypical G protein-coupled receptor that mediates many hormonal responses, including cardiovascular and pulmonary function. β-Agonists used to combat hypercontractility in airway smooth muscle stimulate β2AR-dependent cAMP production that ultimately promote...