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A potent α/β-peptide analogue of GLP-1 with prolonged action in vivo
Lisa M Johnson1, Stacey Barrick, Marlies V Hager
1Department of Chemistry, University of Wisconsin , Madison, Wisconsin 53706, United States.
Abstract:
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-modification approach may be useful for developing stabilized analogues of other peptide hormones.
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