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* |
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.