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Of further interest, the 7 newly formed interfacial salt bridges constitutes a structural electrostatic scaffold (Figures 6, 7, 8, 9, 10 and 11) at the binding interface of GLP-1R ECD and semaglutide analogue A747, which consists of three sets of interfacial salt bridges, as shown by three red numbers (1, 2 and 3) within black circles in Figures 9, 10 and 11

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Compound synthesis and formulation The different GLP1-based multi-agonists employed in the study, including GLP1/E, GLP1/GIP dual agonist, and GLP1/GIP/glucagon triagonist, as well as the GLP1 mono-agonist, were synthesized, purified and characterized as extensively reported elsewhere 33,34,35,74

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