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

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5 Citations (Scopus)

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 languageEnglish
Pages (from-to)485-500
Number of pages16
JournalMolecular Cell
Volume80
Issue number3
DOIs
Publication statusPublished - 5 Nov 2020

Keywords

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

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