G_s protein peptidomimetics as allosteric modulators of the β₂-adrenergic receptor.

ABSTRACT: A series of G_s protein peptidomimetics were designed and synthesised based on the published X-ray crystal structure of the active state β₂-adrenergic receptor (β₂AR) in complex with the G_s protein (PDB 3SN6). We hypothesised that such peptidomimetics may function as allosteric modulators that target the intracellular G_s protein binding site of the β₂AR. Peptidomimetics were designed to mimic the 15 residue C-terminal α-helix of the G_s protein and were pre-organised in a helical conformation by (i, i + 4)-stapling using copper catalysed azide alkyne cycloaddition. Linear and stapled peptidomimetics were analysed by circular dichroism (CD) and characterised in a membrane-based cAMP accumulation assay a

SUBMITTER: Boyhus LE 

PROVIDER: S-EPMC9077236 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature