Table 2.
Stability against DPP-4 catalyzed hydrolysis of native and aza-amino acid containing peptidesa.
| −DPP4 | +DPP4 | ||||||
|---|---|---|---|---|---|---|---|
| Peptide | pEC50 ± SEMb | EC50 (pM)b | n c | pEC50 ± SEMb | EC50 (pMb | n c | Fold-Shift (↓)d |
| GLP-1R | |||||||
| GLP-1, Native | 12 ± 0.07 | 2.2 | 4 | 8.8 ± 0.04 | 1.5 × 103 | 4 | 680 |
| A8AzaA GLP-1 | 11 ± 0.05 | 4.7 | 3 | 11 ± 0.10 | 4.6 | 3 | 0.98 |
| A8AzaG GLP-1 | 11 ± 0.08 | 20 | 3 | 11 ± 0.06 | 20 | 3 | 1.0 |
| A8AzaP GLP-1 | 9.8 ± 0.05 | 160 | 4 | 9.5 ± 0.10 | 310 | 4 | 1.9 |
| G10AzaG GLP-1 | 10 | 7.9 | 1 | 8.1 | 7.4 × 103 | 1 | 940 |
| Semaglutide | 11 ± 0.07 | 19 | 3 | 11 ± 0.06 | 16 | 3 | 0.84 |
| X2AzaA Semaglutide | 10 ± 0.11 | 52 | 3 | 10 ± 0.06 | 42 | 3 | 0.81 |
| X2AzaA X20A DA | 13 ± 0.01 | 0.29 | 3 | 13 ± 0.09 | 0.3 | 3 | 1.0 |
| GIPR | |||||||
| GIP | 11 ± 0. 17 | 6.1 | 3 | 8.9 ± 0.11 | 2.4 × 103 | 3 | 390 |
| A2AzaA GIP | 9.7 ± 0.08 | 210 | 3 | 9.7 ± 0.19 | 210 | 3 | 1.0 |
a
Potencies determined using HEK-293 cells expressing GLP-1R or GIPR with the luciferase reporter system. Results are separated by the targeted receptor. Peptides were incubated at 37 °C overnight with and without DPP4 before their incubation with transfected cells.
b
EC50 = [peptide] required for half maximal activity of the targeted receptor. pEC50 = −log(EC50) ± SEM of independent experiments where applicable.
c
Number of independent experiments.
d
Ratio = (EC50 with DPP4)/(EC50 without DPP4).