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. 2020 Mar 17;3(2):345–360. doi: 10.1021/acsptsci.0c00022

Table 2. Binding and Signalling Parameter Estimates for Chimeric Peptidesa.

  Equilibrium binding cAMP
β-arrestin-2
  pKi (M) pEC50 (M) Emax (%) log τ/KA (M) pEC50 (M) Emax (%) log τ/KA (M)
GLP-1 7.8 ± 0.1 9.5 ± 0.1 100 9.5 ± 0.1 6.2 ± 0.1 102 ± 5 6.2 ± 0.1
Chi1 8.2 ± 0.2 9.5 ± 0.1 100 9.5 ± 0.1 6.4 ± 0.1 102 ± 6 6.4 ± 0.1
Chi2 8.2 ± 0.1* 10.0 ± 0.1* 100 10.0 ± 0.1* 6.9 ± 0.1* 104 ± 6 6.9 ± 0.1*
Chi3 9.4 ± 0.1* 10.0 ± 0.1* 100 10.0 ± 0.1* 6.9 ± 0.2* 93 ± 5* 6.8 ± 0.1*
Ex4-ala2 9.4 ± 0.1* 10.1 ± 0.1* 100 10.1 ± 0.1* 7.1 ± 0.2* 97 ± 5 6.8 ± 0.1*
Ex4 9.7 ± 0.1* 10.2 ± 0.1* 100 10.1 ± 0.1* 6.9 ± 0.1* 77 ± 3* 7.0 ± 0.1*
GLP-1-gly2 7.1 ± 0.1* 8.8 ± 0.1* 100 8.9 ± 0.1* 5.7 ± 0.1* 87 ± 4* 5.7 ± 0.1*
a

Mean ± SEM parameter estimates from data shown in Figure 1, n = 5 experimental repeats. Binding experiments were performed in HEK293-SNAP-GLP-1R cells, signaling experiments were performed in CHO-K1-βarr2-EA-GLP-1R cells. Signaling parameter estimates were determined from 3-parameter fitting. Emax values are expressed relative to the global maximum for full agonists in each assay; note that all compounds are full agonists for cAMP in this cell model, so Emax was globally constrained to 100% in that assay. *p < 0.05 versus GLP-1, determined by one-way ANOVA with Dunnett’s test.