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

Overview

Journal J Am Chem Soc

Publisher American Chemical Society

Specialty Chemistry

Date 2014 Sep 6

PMID 25191938

Citations 43

Authors

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

Affiliations

Soon will be listed here.

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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