Table 1.
Binding properties of ARBs for the WT‐AT1 receptors and various mutants
| Candesartan | Telmisartan | Eprosartan | ||||
|---|---|---|---|---|---|---|
| Mutation | Ki (nM) | ΔKi | Ki (nM) | ΔKi | Ki (nM) | ΔKi |
| WT‐AT1 receptors | 0.08 ± 0.02 | 1 | 0.5 ± 0.02 | 1 | 3.1 ± 0.5 | 1 |
| V108I | 6.9 ± 1.1 | 86.3 | 63.3 ± 4.4 | 127 | 13.8 ± 0.6 | 4.5 |
| S109T | 70.7 ± 14.4 | 884 | 15.7 ± 0.5 | 31 | 3.9 ± 0.3 | 1.3 |
| Y113A | 45.7 ± 11.7 | 571 | 56.8 ± 7.8 | 114 | 16.4 ± 7.0 | 5.3 |
| A163T | 0.5 ± 0.1 | 6.3 | 0.05 ± 0.01 | 0.1 | 2.9 ± 0.8 | 0.9 |
| E173A | 0.2 ± 0.01 | 2.5 | 0.6 ± 0.1 | 1.2 | 3.4 ± 0.2 | 1.1 |
| F182A | 0.3 ± 0.06 | 3.8 | 0.2 ± 0.02 | 0.4 | 4.4 ± 2.1 | 1.4 |
| Y184A | 0.1 ± 0.03 | 1.3 | 0.1 ± 0.03 | 0.2 | 4.1 ± 1.2 | 1.3 |
| K199A | 2.8 ± 0.4 | 35 | 0.4 ± 0.2 | 0.8 | 18.4 ± 0.2 | 5.9 |
| K199Q | 2.3 ± 0.4 | 29 | 1.0 ± 0.3 | 2 | 4.6 ± 0.3 | 1.5 |
| H256A | 0.4 ± 0.1 | 5.0 | 0.4 ± 0.08 | 0.8 | 28.5 ± 1.0 | 9.2 |
| Q257A | 5.6 ± 0.9 | 70 | 16.2 ± 4.2 | 32 | 66.6 ± 12.9 | 21.5 |
| Q257E | 1.2 ± 0.3 | 15 | 2.6 ± 0.3 | 5.2 | 39.9 ± 9.0 | 12.9 |
| Y292A | 0.6 ± 0.2 | 7.5 | 1.3 ± 0.4 | 2.6 | 18.4 ± 0.2 | 5.9 |
| N295A | 5.2 ± 1.0 | 65 | 22.0 ± 4.3 | 44 | 180 ± 10.4 | 58.1 |
| S109T/A163T | 15.0 ± 1.2 | 188 | 0.5 ± 0.09 | 1 | 2.9 ± 0.5 | 0.9 |
| S109T/H256A | 54.8 ± 6.9 | 685 | 0.6 ± 0. 2 | 1.2 | 96.9 ± 7.8 | 31.3 |
| S109T/N295A | 3183 ± 365 | 39 787 | 50.9 ± 4.1 | 102 | 392 ± 110 | 127 |
| A163T/H256A | 0.3 ± 0.02 | 3.8 | 0.03 ± 0.01 | 0.06 | 44.8 ± 3.1 | 14.5 |
| A163T/N295A | 16.0 ± 4.5 | 200 | 6.3 ± 1.3 | 12.6 | 168 ± 45.4 | 54.2 |
| K199Q/H256A | 2.1 ± 0.4 | 26 | 2.3 ± 1.2 | 4.6 | 1335 ± 213 | 431 |
| H256A/N295A | 0.3 ± 0.2 | 3.8 | 8.4 ± 1.6 | 16.8 | 582 ± 6.7 | 188 |
Ligand binding properties for WT‐AT1 receptors and various mutants. Values are presented as mean ± SEM of at least three independent experiments performed in duplicate. The effect of the mutations on the binding affinity is expressed as ΔKi = Ki (mutant)∕Ki (WT‐AT1 receptor).