Table 2.
Binding Affinity (IC50, nM) and cAMP Activity (EC50, nM) of Cyclic Melanotropin Peptides at Various Human Melanocortin Receptors
|
hMC1R |
hMC3R |
hMC4R |
hMC5R |
|||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| peptide | IC50a (nM) | binding eff. (%)c | EC50b (nM) | act. % | IC50a (nM) | binding eff. (%)c | EC50b (nM) | act. % | IC50a (nM) | binding eff. (%)c | EC50b (nM) | act. % | IC50a (nM) | binding eff. (%)c | EC50b (nM) | act. % |
| MTII | 0.20±0.01 | 100 | 0.30±0. 04 | 100 | 2±0.2 | 100 | 1.9 ±0.2 | 100 | 1.1±0.3 | 100 | 2.9±0. 52 | 100 | 7.5±0.2 | 100 | 3.3±0.7 | 100 |
| 1 | NB | 0 | NA | 0 | NB | 0 | NA | 0 | 1.8±0.4 | 50 | NA | 0 | NB | 0 | NA | 0 |
| 2 | 1000 | <10 | NA | 0 | NB | 0 | NA | 0 | NB | 0 | NA | 0 | NB | 0 | NA | 0 |
| 3 | >1000 | <10 | NA | 0 | >1000 | 50 | NA | 0 | 4.1±1 | 50 | >1000 | 18 | NB | 0 | NA | 0 |
| 4 | NB | 0 | NA | 0 | >1000 | <10 | NA | 0 | 0.7±0.1 | 50 | >1000 | 19 | NB | 0 | NA | 0 |
| 5 | >1000 | <10 | NA | 0 | >1000 | 50 | NA | 0 | NB | 0 | NA | 0 | NB | 0 | NA | 0 |
| 6 | 750±100 | <10 | NA | 0 | >1000 | 50 | NA | 0 | 101±20 | 50 | >1000 | <10 | NB | 0 | NA | 0 |
| 7 | >1000 | <10 | NA | 0 | NB | 0 | NA | 0 | NB | 0 | NA | 0 | 209±30 | <10 | NA | 0 |
| 8 | >10000 | <10 | NA | 0 | >1000 | 50 | NA | 0 | NB | 0 | NA | 0 | NB | 0 | NA | 0 |
IC50 = Concentration of peptide at 50% specific binding (N = 4–6). The peptides were tested in a range of concentrations (10−10 to 10−5 M).
EC50 = Concentration of peptide at 50% maximal cAMP generation (n = 4). The peptides were tested in a range of concentrations (10−10 to 10−5 M).
Binding efficiency: maximal percentage binding of test compounds vs MTII agonist binding when competed with [125I]NDP-α-MSH. NB = No binding; NA = no cAMP activity. Three experiments were done in duplicate (n = 6) for binding as well as cAMP assays.