A Potent α/β-Peptide Analogue of GLP‑1 with Prolonged Action in Vivo

Glucagon-like peptide-1 (GLP-1) is a natural agonist for GLP-1R, a G protein-coupled receptor (GPCR) on the surface of pancreatic β cells. GLP-1R agoinsts are attractive for treatment of type 2 diabetes, but GLP-1 itself is rapidly degraded by peptidases <i>in vivo</i>. We describe a design strategy for retaining GLP-1-like activity while engendering prolonged activity <i>in vivo</i>, based on strategic replacement of native α residues with conformationally constrained β-amino acid residues. This backbone-modification approach may be useful for developing stabilized analogues of other peptide hormones