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Further fatty acid modification with γGlu-palmitic acid side chain at position 14 afforded peptide 13 (Figure 13) with increased agonistic activity for both GLP-1R and GCGR (EC 50 values of 0.024 nM (GLP-1R), and 0.082 nM (GCGR) in GLP-1R activation assay measured by cAMP accumulation), and resulting equipotent to liraglutide against GLP-1R (EC 50 values of 0.018 nM), and two-fold more potent than cotadutide (EC 50 values of 0.051 nM)

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doi: 10.1016/j.micpath.2020.104454 9 JiangJWuCGaoHSongJLiH