Figure 4.

Representative concentration–response curves of unmodified peptides (GLP1, liraglutide, GIP, and glucagon; a–d) or N-trifluoroethyl analogues (2-GLP1, 2-liraglutide, 2-GIP, and 2-glucagon; e–h) incubated overnight with DPP4 or vehicle prior to diluting into microtiter plates containing HEK293 cells overly expressing receptors (GLP1R, GIPR, or GCGR) and reporter CRE_6x-luciferase. Luciferase production corresponds directly to activation of cognate GPCR via a cAMP dependent pathway, normalized to 100% maximal activity, and resultant fold-loss in EC₅₀ upon DPP4 incubation is listed when applicable. Error bars represent SEM for three independent experiments (n = 3).