β-Arrestin-Biased Agonists of the GLP-1 Receptor from β-Amino Acid Residue Incorporation into GLP-1 Analogues.

ABSTRACT: Activation of a G protein-coupled receptor (GPCR) causes recruitment of multiple intracellular proteins, each of which can activate distinct signaling pathways. This complexity has engendered interest in agonists that preferentially stimulate subsets among the natural signaling pathways ("biased agonists"). We have examined analogues of glucagon-like peptide-1 (GLP-1) containing β-amino acid residues in place of native α residues at selected sites and found that some analogues differ from GLP-1 in terms of their relative abilities to promote G protein activation (as monitored via cAMP production) versus β-arrestin recruitment (as monitored via BRET assays). The α → β replacements generally cause modest declines in stimulation of cAMP production and β-arrestin recruitment, but for some repl

SUBMITTER: Hager MV 

PROVIDER: S-EPMC5207657 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature