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

Lisa M. Johnson, Stacey Barrick, Marlies V. Hager, Amanda McFedries, Edwin A. Homan, Mary E. Rabaglia, Mark P. Keller, Alan D. Attie, Alan Saghatelian, Alessandro Bisello, Samuel H. Gellman

Research output: Contribution to journalArticlepeer-review

59 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)12848-12851
Number of pages4
JournalJournal of the American Chemical Society
Volume136
Issue number37
DOIs
StatePublished - Sep 5 2015

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Publisher Copyright:
© 2014 American Chemical Society.

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