Differential GLP-1R Binding and Activation by Peptide and Non-peptide Agonists

Xin Zhang; Matthew J. Belousoff; Peishen Zhao; Albert J. Kooistra; Tin T. Truong; Sheng Yu Ang; Christina Rye Underwood; Thomas Egebjerg; Petr Šenel; Gregory D. Stewart; Yi Lynn Liang; Alisa Glukhova; Hari Venugopal; Arthur Christopoulos; Sebastian G.B. Furness; Laurence J. Miller; Steffen Reedtz-Runge; Christopher J. Langmead; David E. Gloriam; Radostin Danev; Patrick M. Sexton; Denise Wootten

doi:10.1016/j.molcel.2020.09.020

Differential GLP-1R Binding and Activation by Peptide and Non-peptide Agonists

Xin Zhang, Matthew J. Belousoff, Peishen Zhao, Albert J. Kooistra, Tin T. Truong, Sheng Yu Ang, Christina Rye Underwood, Thomas Egebjerg, Petr Šenel, Gregory D. Stewart, Yi Lynn Liang, Alisa Glukhova, Hari Venugopal, Arthur Christopoulos, Sebastian G.B. Furness, Laurence J. Miller, Steffen Reedtz-Runge, Christopher J. Langmead, David E. Gloriam, Radostin DanevPatrick M. Sexton, Denise Wootten

Gastroenterology and Hepatology

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

12 Scopus citations

Abstract

Zhang et al. show that the non-peptide GLP-1R agonist PF 06882961, but not CHU-128, was able to closely mimic the in vitro pharmacological fingerprint of GLP-1. These pharmacological activities could be rationalized from high-resolution structures that provide a novel template for the design of new agonists targeting the GLP-1R.

Original language	English (US)
Pages (from-to)	485-500.e7
Journal	Molecular Cell
Volume	80
Issue number	3
DOIs	https://doi.org/10.1016/j.molcel.2020.09.020
State	Published - Nov 5 2020

Keywords

G-protein-coupled receptor
GLP-1
cryoelectron microscopy
glucagon-like peptide-1 receptor
non-peptide agonists

ASJC Scopus subject areas

Molecular Biology
Cell Biology

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10.1016/j.molcel.2020.09.020

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Zhang, X., Belousoff, M. J., Zhao, P., Kooistra, A. J., Truong, T. T., Ang, S. Y., Underwood, C. R., Egebjerg, T., Šenel, P., Stewart, G. D., Liang, Y. L., Glukhova, A., Venugopal, H., Christopoulos, A., Furness, S. G. B., Miller, L. J., Reedtz-Runge, S., Langmead, C. J., Gloriam, D. E., ... Wootten, D. (2020). Differential GLP-1R Binding and Activation by Peptide and Non-peptide Agonists. Molecular Cell, 80(3), 485-500.e7. https://doi.org/10.1016/j.molcel.2020.09.020

Zhang, X, Belousoff, MJ, Zhao, P, Kooistra, AJ, Truong, TT, Ang, SY, Underwood, CR, Egebjerg, T, Šenel, P, Stewart, GD, Liang, YL, Glukhova, A, Venugopal, H, Christopoulos, A, Furness, SGB, Miller, LJ, Reedtz-Runge, S, Langmead, CJ, Gloriam, DE, Danev, R, Sexton, PM & Wootten, D 2020, 'Differential GLP-1R Binding and Activation by Peptide and Non-peptide Agonists', Molecular Cell, vol. 80, no. 3, pp. 485-500.e7. https://doi.org/10.1016/j.molcel.2020.09.020

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abstract = "Zhang et al. show that the non-peptide GLP-1R agonist PF 06882961, but not CHU-128, was able to closely mimic the in vitro pharmacological fingerprint of GLP-1. These pharmacological activities could be rationalized from high-resolution structures that provide a novel template for the design of new agonists targeting the GLP-1R.",

keywords = "G-protein-coupled receptor, GLP-1, cryoelectron microscopy, glucagon-like peptide-1 receptor, non-peptide agonists",

author = "Xin Zhang and Belousoff, {Matthew J.} and Peishen Zhao and Kooistra, {Albert J.} and Truong, {Tin T.} and Ang, {Sheng Yu} and Underwood, {Christina Rye} and Thomas Egebjerg and Petr {\v S}enel and Stewart, {Gregory D.} and Liang, {Yi Lynn} and Alisa Glukhova and Hari Venugopal and Arthur Christopoulos and Furness, {Sebastian G.B.} and Miller, {Laurence J.} and Steffen Reedtz-Runge and Langmead, {Christopher J.} and Gloriam, {David E.} and Radostin Danev and Sexton, {Patrick M.} and Denise Wootten",

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year = "2020",

month = nov,

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doi = "10.1016/j.molcel.2020.09.020",

language = "English (US)",

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AU - Belousoff, Matthew J.

AU - Zhao, Peishen

AU - Kooistra, Albert J.

AU - Truong, Tin T.

AU - Ang, Sheng Yu

AU - Underwood, Christina Rye

AU - Egebjerg, Thomas

AU - Šenel, Petr

AU - Stewart, Gregory D.

AU - Liang, Yi Lynn

AU - Glukhova, Alisa

AU - Venugopal, Hari

AU - Christopoulos, Arthur

AU - Furness, Sebastian G.B.

AU - Miller, Laurence J.

AU - Reedtz-Runge, Steffen

AU - Langmead, Christopher J.

AU - Gloriam, David E.

AU - Danev, Radostin

AU - Sexton, Patrick M.

AU - Wootten, Denise

PY - 2020/11/5

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Differential GLP-1R Binding and Activation by Peptide and Non-peptide Agonists

Abstract

Keywords

ASJC Scopus subject areas

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