Journal article
Differential GLP-1R Binding and Activation by Peptide and Non-peptide Agonists
X Zhang, MJ Belousoff, P Zhao, AJ Kooistra, TT Truong, SY Ang, CR Underwood, T Egebjerg, P Šenel, GD Stewart, YL Liang, A Glukhova, H Venugopal, A Christopoulos, SGB Furness, LJ Miller, S Reedtz-Runge, CJ Langmead, DE Gloriam, R Danev Show all
Molecular Cell | CELL PRESS | Published : 2020
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.
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Grants
Awarded by Takeda Science Foundation
Funding Acknowledgements
This work was supported by the National Health and Medical Research Council of Australia (NHMRC) (nos. 1126857, 1184726, 1160076, and 1150083). P.M.S. is a Senior Principal Research Fellow and D.W. a Senior Research Fellow of the NHMRC. R.D. was supported by Takeda Science Foundation 2019 Medical Research Grant and Japan Science and Technology Agency PRESTO (18069571). D.E.G. was funded by the Lundbeck Foundation (R163-2013-16327) and A.J.K. from the Independent Research Fund Denmark (8021-00173B). This work was partially supported by the Monash University Ramaciotti Centre for cryoelectron microscopy and the Monash University MASSIVE high-performance computing facility.