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

doi:10.1021/ja507168t

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

Laboratory Medicine and Pathology

Research output: Contribution to journal › Article › peer-review

84 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 language	English (US)
Pages (from-to)	12848-12851
Number of pages	4
Journal	Journal of the American Chemical Society
Volume	136
Issue number	37
DOIs	https://doi.org/10.1021/ja507168t
State	Published - Sep 5 2015

Bibliographical note

Publisher Copyright:
© 2014 American Chemical Society.

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Publisher link

10.1021/ja507168t

Find It

Find It at U of M Libraries

Cite this

@article{b93ec4b607884cb892c86065e169564b,

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

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.",

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

note = "Publisher Copyright: {\textcopyright} 2014 American Chemical Society.",

year = "2015",

month = sep,

day = "5",

doi = "10.1021/ja507168t",

language = "English (US)",

volume = "136",

pages = "12848--12851",

journal = "Journal of the American Chemical Society",

issn = "0002-7863",

publisher = "American Chemical Society",

number = "37",

}

TY - JOUR

T1 - A Potent α/β-Peptide Analogue of GLP-1 with Prolonged Action in Vivo

AU - Johnson, Lisa M.

AU - Barrick, Stacey

AU - Hager, Marlies V.

AU - McFedries, Amanda

AU - Homan, Edwin A.

AU - Rabaglia, Mary E.

AU - Keller, Mark P.

AU - Attie, Alan D.

AU - Saghatelian, Alan

AU - Bisello, Alessandro

AU - Gellman, Samuel H.

PY - 2015/9/5

Y1 - 2015/9/5

N2 - 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.

AB - 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.

UR - https://www.scopus.com/pages/publications/84919945753

UR - https://www.scopus.com/pages/publications/84919945753#tab=citedBy

U2 - 10.1021/ja507168t

DO - 10.1021/ja507168t

M3 - Article

C2 - 25191938

AN - SCOPUS:84919945753

SN - 0002-7863

VL - 136

SP - 12848

EP - 12851

JO - Journal of the American Chemical Society

JF - Journal of the American Chemical Society

IS - 37

ER -

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

Abstract

Bibliographical note

UN SDGs

Publisher link

Find It

Other files and links

Fingerprint

Cite this