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

  title={A Potent
α/β-Peptide Analogue of GLP-1
with Prolonged Action in Vivo},
  author={Lisa M. Johnson and Stacey Barrick and Marlies V Hager and Amanda K. McFedries and Edwin A. Homan and Mary E. Rabaglia and Mark P Keller and Alan D Attie and Alan Saghatelian and Alessandro Bisello and Samuel H. Gellman},
  booktitle={Journal of the American Chemical Society},
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 in vivo. We describe a design strategy for retaining GLP-1-like activity while engendering prolonged activity in vivo, based on strategic replacement of native α residues with conformationally constrained β-amino acid residues. This backbone… CONTINUE READING
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