Affinity estimates (pKI) for PAMs at mGlu5-wt and mutants from inhibition binding assays
Data represent the mean ± S.E.M. of a minimum of three independent determinations.
| Mutation | VU0360172 (Nicotinamide) | VU0403602 (Picolinamide) | VU0360173 (Nicotinamide) | VU0405398 (Picolinamide) | VU0415051 (Nicotinamide) | VU0405386 (Picolinamide) |
|---|---|---|---|---|---|---|
| R5-wt (low) | 6.57 ± 0.02# | 8.26 ± 0.15 | 5.12 ± 0.07 | 6.05 ± 0.12# | 6.88 ± 0.04# | 7.98 ± 0.05# |
| I650A | N.D. | 7.89 ± 0.10 | 5.30 ± 0.26 | 6.41 ± 0.14 | 6.62 ± 0.11 | 7.69 ± 0.15 |
| P742S | 5.90 ± 0.12* | 7.24 ± 0.23* | 5.12 ± 0.27 | 5.78 ± 0.14 | 6.35 ± 0.13* | 7.19 ± 0.12* |
| L743V | 6.32 ± 0.06 | 6.98 ± 0.10* | 4.86 ± 0.08 | 5.71 ± 0.01* | 6.25 ± 0.17* | 7.58 ± 0.04 |
| N746A | 6.22 ± 0.07 | 7.49 ± 0.07* | 4.63 ± 0.10 | 5.75 ± 0.03 | 6.35 ± 0.26* | 7.45 ± 0.30 |
| G747V | 6.76 ± 0.05 | N.D. | N.D. | N.D. | 7.06 ± 0.27 | 8.17 ± 0.35 |
| V788A | 7.08 ± 0.23 | 8.70 ± 0.02 | 6.10 ± 0.09* | 7.87 ± 0.05* | 8.15 ± 0.07* | 9.20 ± 0.10* |
| F792A | 7.06 ± 0.15 | 7.85 ± 0.04 | 5.68 ± 0.06 | 6.74 ± 0.08* | 7.09 ± 0.06 | 7.71 ± 0.19 |
| C815A | 6.74 ± 0.24 | 8.01 ± 0.03 | 5.01 ± 0.07 | 6.26 ± 0.04 | 6.92 ± 0.11 | 7.96 ± 0.16 |
N.D., not determined.
↵* P < 0.05 vs. wild-type receptor, one-way analysis of variance (ANOVA), Dunnett’s post-test; #data previously reported (Gregory et al., 2012).