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The structure of two previously discovered potent GLP-1R/GIPR dual agonists (peptides 34 – 35 , Figure 25) (Jing, 2023) was used as template to design this new series by (i) connecting either peptide 34 or 35 to PYY-2 analogue (see Figure 15), and introducing a cysteine residue at the C-terminus of 34 or 35 , and a 3-maleimidopropionic acid at the OEG junction of the N-terminus of the PYY-2 analogue
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