Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Can Semaglutide Bind Tighter to GLP-1R?

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Version 1 : Received: 23 July 2020 / Approved: 24 July 2020 / Online: 24 July 2020 (11:58:41 CEST)

How to cite: Li, W. Can Semaglutide Bind Tighter to GLP-1R?. Preprints 2020, 2020070582. Li, W. Can Semaglutide Bind Tighter to GLP-1R?. Preprints 2020, 2020070582.


Semaglutide is a glucagon-like peptide 1 analog used for the treatment of patients with type 2 diabetes mellitus. With 94% sequence similarity to human GLP-1, semaglutide is a glucagon-like peptide-1 receptor (GLP-1R) agonist, which binds directly to GLP-1R, causing various beneficial downstream effects that reduce blood glucose. Practically, it is favourable for semaglutide to bind not just directly, but also tighter, to its receptor GLP-1R. Therefore, incorporating currently available experimental structural data of semaglutide-GLP-1R, this short article reports for the first time that biophysically, semaglutide is able to bind tighter to GLP-1R with just a simple Val27-Arg28 exchange in its peptide backbone.


Semaglutide; GLP-1R; Interfacial Biophysics


Biology and Life Sciences, Biophysics

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