Table 2. Binding affinities of monovalent and bivalent ligands for hMC4R.
ligand | Structure | aLogEC50 | bEC50 (nM) | Hill coefficient |
---|---|---|---|---|
1 | Ac-(Pro-Gly)6-SHU9119-NH2 | -8.40 ± 0.06 | 4.0 | 1.1 |
2 | Ac-(Pro-Gly)9-SHU9119-NH2 | -8.09 ± 0.05 | 8.1 | 0.8 |
3 | Ac-(Pro-Gly)12-SHU9119-NH2 | -7.88 ± 0.17 | 13 | 1.1 |
4 | Ac-PEGO-(Pro-Gly)3-PEGO-SHU9119-NH2 | -8.43 ± 0.06 | 3.7 | 0.9 |
5 | Ac- PEGO-SHU9119-NH2 | -7.60 ± 0.51 | 24 | 0.6 |
6 | Ac- PEGO-PEGO-SHU9119-NH2 | -6.39 ± 0.46 | 400 | 0.8 |
7 | Ac-SHU9119-(Pro-Gly)6-SHU9119-NH2 | N.D | N.D | - |
8 | Ac-SHU9119-(Pro-Gly)9-SHU9119-NH2 | -8.81 ± 0.02 | 1.6 | 2.2 |
9 | Ac-SHU9119-(Pro-Gly)12-SHU9119-NH2 | -8.71 ± 0.02 | 2.0 | 3.0 |
10 | Ac-SHU9119-PEGO-(Pro-Gly)3-PEGO-SHU9119-NH2 | -8.67 ± 0.02 | 2.2 | 1.9 |
11 | Ac-SHU9119-PEGO-SHU9119-NH2 | -8.74 ± 0.06 | 1.8 | 2.2 |
12 | Ac-SHU9119-PEGO-PEGO-SHU9119-NH2 | -8.73 ± 0.02 | 1.9 | 1.9 |
13 | Ac-MSH(7)-(Pro-Gly)6-SHU9119-NH2 | -8.39 ± 0.12 | 4.1 | 0.7 |
14 | Ac-MSH(7)-(Pro-Gly)9-SHU9119-NH2 | -8.71 ± 0.08 | 2.0 | 0.8 |
15 | Ac-MSH(7)-(Pro-Gly)12-SHU9119-NH2 | -8.80 ± 0.04 | 1.6 | 2.0 |
16 | Ac-MSH(7)-PEGO-(Pro-Gly)3-PEGO-SHU9119-NH2 | -8.86 ± 0.03 | 1.3 | 2.4 |
17 | Ac-MSH(7)-PEGO-SHU9119-NH2 | -8.73 ± 0.02 | 1.4 | 2.7 |
18 | Ac-MSH(7)-PEGO-PEGO-SHU9119-NH2 | -8.77 ± 0.02 | 1.7 | 2.7 |
19 | Ac-(Pro-Gly)6- MSH(7)-NH2 | 82 ± 12c | ||
20 | Ac-(Pro-Gly)9- MSH(7)-NH2 | 236 ± 24c | ||
21 | Ac-(Pro-Gly)12- MSH(7)-NH2 | 188 ± 25c | ||
22 | Ac-MSH(7)-(Pro-Gly)6- MSH(7)-NH2 | 11 ± 2c |
The logEC50 ± SEM are logarithmic values determined from the nonlinear regression analysis of data collected from 4 independent concentration range.
Determined from Dissociation Enhanced Lanthanide FluoroImmuno Assay (DELFIA) using optimized 10 nM standard agonist Eu-DTPA-NDP-α-MSH chelate.
see reference 3