Table 2:
Tetrapeptide agonist pharmacology at the mouse melanocortin receptors.a
| Peptide | Compound ID |
Sequence | EC50 (nM) | |||
|---|---|---|---|---|---|---|
| mMC1R | mMC3R | mMC4R | mMC5R | |||
| NDP-MSH | 0.010±0.001 | 0.079±0.008 | 0.72±0.08 | 0.19±0.008 | ||
| 1 | LTT1-20 | Ac-DPhe(pI)-Arg-Nal(2’)-Arg-NH2 | 35% @ 100 μM | >100,000 | 25% @ 100 μM | >100,000 |
| 2 | LTT1-24 | Ac-DPhe(pI)-His-Nal(2’)-Arg-NH2 | 20% @ 100 μM | >100,000 | >100,000 | >100,000 |
| 3 | LTT1-16 | Ac-DPhe(pI)-Lys-Nal(2’)-Arg-NH2 | 20% @ 100 μM | >100,000 | >100,000 | >100,000 |
| 4 | LTT1-28 | Ac-DPhe(pI)-Orn-Nal(2’)-Arg-NH2 | 20% @ 100 μM | >100,000 | >100,000 | >100,000 |
| 5 | LTT1-32 | Ac-DPhe(pI)-Dab-Nal(2’)-Arg-NH2 | >100,000 | >100,000 | >100,000 | >100,000 |
| 6 | LTT1-36 | Ac-DPhe(pI)-Dap-Nal(2’)-Arg-NH2 | >100,000 | >100,000 | >100,000 | >100,000 |
| 7 | LTT1-40 | Ac-DPhe(pI)-hArg-Nal(2’)-Arg-NH2 | 25% @ 100 μM | >100,000 | >100,000 | >100,000 |
| 8 | LTT1-44 | Ac-DPhe(pI)-DArg-Nal(2’)-Arg-NH2 | 25% @ 100 μM | >100,000 | >100,000 | >100,000 |
| 9 | LTT1-52 | Ac-DPhe(pI)-DLys-Nal(2’)-Arg-NH2 | >100,000 | >100,000 | >100,000 | >100,000 |
| 10 | LTT1-48-4 | Ac-DPhe(pI)-Cit-Nal(2’)-Arg-NH2 | 40% @ 100 μM | >100,000 | >100,000 | >100,000 |
| 11 | LTT1-56-2 | Ac-DPhe(pI)-Glu-Nal(2’)-Arg-NH2 | >100,000 | >100,000 | >100,000 | >100,000 |
| 12 | SSM1-6 | Ac-DPhe(pI)-Arg-Nal(2’)-His-NH2 | Partial Agonist 400±100 55%NDP |
35% @ 100 μM | >100,000 | >100,000 |
| 13 | SSM1-3P1 | Ac-DPhe(pI)-Arg-Nal(2’)-Lys-NH2 | 30% @ 100 μM | >100,000 | >100,000 | >100,000 |
| 14 | SSM1-8 | Ac-DPhe(pI)-Arg-Nal(2’)-Orn-NH2 | Partial Agonist 3000±1000 40%NDP |
>100,000 | >100,000 | >100,000 |
| 15 | SSM1-10 | Ac-DPhe(pI)-Arg-Nal(2’)-Dab-NH2 | Partial Agonist 1100±600 55%NDP |
>100,000 | >100,000 | >100,000 |
| 16 | SSM1-12 | Ac-DPhe(pI)-Arg-Nal(2’)-Dap-NH2 | 30% @ 100 μM | >100,000 | >100,000 | >100,000 |
| 17 | SSM1-14 | Ac-DPhe(pI)-Arg-Nal(2’)-hArg-NH2 | 40% @ 100 μM | >100,000 | >100,000 | >100,000 |
| 18 | SSM1-16 | Ac-DPhe(pI)-Arg-Nal(2’)-DArg-NH2 | >100,000 | >100,000 | >100,000 | >100,000 |
| 19 | SSM1-18 | Ac-DPhe(pI)-Arg-Nal(2’)-DLys-NH2 | >100,000 | >100,000 | >100,000 | >100,000 |
| 20 | SSM1-20 | Ac-DPhe(pI)-Arg-Nal(2’)-Cit-NH2 | >100,000 | >100,000 | >100,000 | >100,000 |
| 21 | JLB1-3 | Ac-DPhe(pI)-Arg-Nal(2’)-Glu-NH2 | >100,000 | >100,000 | >100,000 | >100,000 |
a
The indicated errors represent the standard error of the mean from at least three independent experiments. A percentage denotes the percent maximal stimulatory response (compared to NDP-MSH) observed at 100 μM, but not enough stimulation was observed to determine an EC50 value. The use of >100,000 indicates that the compound was examined but lack agonist activity at concentrations up to 100 μM in at least two independent experiments. Tetrapeptides labeled partial agonists were observed to possess partial agonist activity, with the apparent EC50 values and percentage of receptor activation relative to NDP-MSH.