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J Am Chem Soc. 2014 Sep 17;136(37):12848-51. doi: 10.1021/ja507168t. Epub 2014 Sep 5.

A potent α/β-peptide analogue of GLP-1 with prolonged action in vivo.

Author information

1
Department 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.

PMID:
25191938
PMCID:
PMC4183665
DOI:
10.1021/ja507168t
[Indexed for MEDLINE]
Free PMC Article

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