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

[Image: see text] 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 desi...

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Autores principales: Johnson, Lisa M., Barrick, Stacey, Hager, Marlies V., McFedries, Amanda, Homan, Edwin A., Rabaglia, Mary E., Keller, Mark P., Attie, Alan D., Saghatelian, Alan, Bisello, Alessandro, Gellman, Samuel H.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2014
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4183665/
https://www.ncbi.nlm.nih.gov/pubmed/25191938
http://dx.doi.org/10.1021/ja507168t
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author Johnson, Lisa M.
Barrick, Stacey
Hager, Marlies V.
McFedries, Amanda
Homan, Edwin A.
Rabaglia, Mary E.
Keller, Mark P.
Attie, Alan D.
Saghatelian, Alan
Bisello, Alessandro
Gellman, Samuel H.
author_facet Johnson, Lisa M.
Barrick, Stacey
Hager, Marlies V.
McFedries, Amanda
Homan, Edwin A.
Rabaglia, Mary E.
Keller, Mark P.
Attie, Alan D.
Saghatelian, Alan
Bisello, Alessandro
Gellman, Samuel H.
author_sort Johnson, Lisa M.
collection PubMed
description [Image: see text] 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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spelling pubmed-41836652015-09-05 A Potent α/β-Peptide Analogue of GLP-1 with Prolonged Action in Vivo Johnson, Lisa M. Barrick, Stacey Hager, Marlies V. McFedries, Amanda Homan, Edwin A. Rabaglia, Mary E. Keller, Mark P. Attie, Alan D. Saghatelian, Alan Bisello, Alessandro Gellman, Samuel H. J Am Chem Soc [Image: see text] 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. American Chemical Society 2014-09-05 2014-09-17 /pmc/articles/PMC4183665/ /pubmed/25191938 http://dx.doi.org/10.1021/ja507168t Text en Copyright © 2014 American Chemical Society Terms of Use (http://pubs.acs.org/page/policy/authorchoice_termsofuse.html)
spellingShingle Johnson, Lisa M.
Barrick, Stacey
Hager, Marlies V.
McFedries, Amanda
Homan, Edwin A.
Rabaglia, Mary E.
Keller, Mark P.
Attie, Alan D.
Saghatelian, Alan
Bisello, Alessandro
Gellman, Samuel H.
A Potent α/β-Peptide Analogue of GLP-1 with Prolonged Action in Vivo
title A Potent α/β-Peptide Analogue of GLP-1 with Prolonged Action in Vivo
title_full A Potent α/β-Peptide Analogue of GLP-1 with Prolonged Action in Vivo
title_fullStr A Potent α/β-Peptide Analogue of GLP-1 with Prolonged Action in Vivo
title_full_unstemmed A Potent α/β-Peptide Analogue of GLP-1 with Prolonged Action in Vivo
title_short A Potent α/β-Peptide Analogue of GLP-1 with Prolonged Action in Vivo
title_sort potent α/β-peptide analogue of glp-1 with prolonged action in vivo
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4183665/
https://www.ncbi.nlm.nih.gov/pubmed/25191938
http://dx.doi.org/10.1021/ja507168t
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