Work

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

Year: 2014

Type: article

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.

Source: Journal of the American Chemical Society

DOI: 10.1021/ja507168t

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

Institutions: University of Wisconsin–Madison, University of Pittsburgh, Harvard University

Language: English

Topic: Chemical Synthesis and Analysis

Subfield: Organic Chemistry

Field: Chemistry

Domain: Physical Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $4,500

Funders: American Diabetes Association, National Institute of General Medical Sciences, National Institute of Diabetes and Digestive and Kidney Diseases

Awards: Novel Agonists and Inverse Agonists for B-Family GPCRs, G3344537491, NK CELL ADCC AND CD4+ CELL APOPTOSIS IN HIV+ TISSUES, The Genetics of Obesity and Diabetes, Chemistry-Biology Interface Training Program

OpenAlex ID: W2044865569

FWCI: 6.439

Cites: 44

Cited by: 96

Related to: 10