Table 1.
Functional activity of the modified peptides at the mouse melanocortin receptors
| mMC1R | mMC3R | mMC4R | mMC5R | hMC5R | ||
|---|---|---|---|---|---|---|
| Peptide | Structure | EC50 (nM) | EC50 (nM) | EC50 (nM) | EC50 (nM) | EC50 (nM) |
| α-MSH | Ac-Ser-Tyr-Ser-Met-Glu-His-Phe-Arg-Trp-Gly-Lys-Pro-Val-NH2 | 0.70±0.23 | 2.10±0.46 | 2.6±0.29 | 2.00±0.20 | |
| NDP-MSH | Ac-Ser-Tyr-Ser-Nle-Glu-His-DPhe-Arg-Trp-Gly-Lys-Pro-Val-NH2 | 1.0±0.78 | 0.09±0.02 | 0.10±0.01 | 0.22±0.03 | 0.53±0.10 |
| γ2-MSH (Bachem control) |
Tyr-Val-Met-Gly-His-Phe-Arg-Trp-Asp-Arg-Phe-Gly | 680±190 | 38±6.5 | 420±68 | 42±14 | 2700±900 |
| 1 γ2-MSH | Tyr-Val-Met-Gly-His-Phe-Arg-Trp-Asp-Arg-Phe-Gly | 690±260 | 51±5.3 | 580±160 | 73±14 | 2600±620 |
| 2 | Tyr-Val-Met-Gly-His-Phe-Arg-DTrp8-Asp-Arg-Phe-Gly | 120±44 | 90±46 | 5580±2300 | 48±20 | 580±280 |
| 3 | Tyr-Val-Nle3-Gly-His-Phe-Arg-Trp-Asp-Arg-Phe-Gly | 390±90 | 68±30 | 270±82 | 140±80 | 1900±620 |
| 4 | Tyr-Val-Nle3-Gly-His-Phe-Arg-DTrp8-Asp-Arg-Phe-Gly | 31±11 | 40±20 | 94±33 | 10±1.7 | 210±58 |
| 5 | Tyr-Val-Met-Gly-His-Phe-Arg-Trp-Asp-Arg-Phe (1-11) | 1500±90 | 160±10 | 1100±78 | 130±52 | 2010±460 |
| 6 | Tyr-Val-Met-Gly-His-Phe-Arg-Trp-Asp-Arg (1-10) | 250±60 | 36±9.2 | 660±190 | 62±23 | 7360±2300 |
| 7 | Tyr-Val-Met-Gly-His-Phe-Arg-Trp-Asp (1-9) | 430±90 | 800±96 | 1380±470 | 73±17 | 4455±1510 |
| 8 | Tyr-Val-Met-Gly-His-Phe-Arg-Trp (1-8) | 2900±960 | 2800±950 | 4200±590 | 710±160 | 23900±8600 |
| 9 | Tyr-Val-Met-Gly-His-Phe-Arg- (1-7) | 28100±6700 | 31600±2100 | >100000 | 2360±13600 | >100000 |
| 10 | Tyr-Val-Met-Gly-His-Phe (1-6) | >100000 | >100000 | >100000 | >100000 | >100000 |
| 11 | Tyr-Val-Met-Gly-His (1-5) | 60%@100μM | >100000 | 25%@100μM | 26800±3400 | |
| 12 | Tyr-Val-Met-Gly (1-4) | >100000 | >100000 | >100000 | >100000 | |
| 13 | Tyr-Val-Met-OH (1-3) | >100000 | >100000 | >100000 | >100000 | |
| 14 | Val-Met-Gly-His-Phe-Arg-Trp-Asp-Arg-Phe-Gly (2-12) | 1260±480 | 400±250 | 830±350 | 81±32 | |
| 15 | Met-Gly-His-Phe-Arg-Trp-Asp-Arg-Phe-Gly (3-12) | 1590±520 | 260±67 | 1200±460 | 94±14 | |
| 16 | Gly-His-Phe-Arg-Trp-Asp-Arg-Phe-Gly (4-12) | 7860±2650 | 760±240 | 2700±550 | 290±150 | |
| 17 | His-Phe-Arg-Trp-Asp-Arg-Phe-Gly (5-12) | 20100±5900 | 2670±100 | 8380±2700 | 760±290 | |
| 18 | Phe-Arg-Trp-Asp-Arg-Phe-Gly (6-12) | 30%@100μM | >100000 | 47400±17700 | 13500±7200 90%@100μM |
|
| 19 | Arg-Trp-Asp-Arg-Phe-Gly (7-12) | >100000 | >100000 | >100000 | >100000 | |
| 20 | Trp-Asp-Arg-Phe-Gly (8-12) | >100000 | >100000 | >100000 | >100000 | |
| 21 | Asp-Arg-Phe-Gly (9-12) | >100000 | >100000 | >100000 | >100000 | |
| 22 | Arg-Phe-Gly (10-12) | >100000 | >100000 | >100000 | >100000 | |
| 23 | Tyr-Met-His-Phe-Arg-Trp-Phe (1,3,5-8,11) | 67100±1110 | 10400±2250 | 14010±3700 | 1100±280 | |
| 24 | Met-Gly-His-Phe-Arg-Trp (3-8) | 14500±2100 | 22400±5200 | 41900±11800 | 4430±3800 | |
| 25 | His-Phe-Arg-Trp-Asp-Arg-Phe (5-11) | 44800±6100 | 6600±700 | 64400±19800 | 1870±620 | |
| 26 | Phe-Arg-Trp-Asp-Arg-Phe (6-11) | 3170±750 | 20400±3300 | 34040±9500 | 6730±1490 | |
| 27 | Met-Gly-His-Phe-Arg-Trp-Asp-Arg-Phe (3-11) | 1770±270 | 365±90 | 2410±860 | 100±23 | |
| 28 | Asp-Arg-Phe (9-11) | >100000 | >100000 | >100000 | >100000 | |
| 29 | His-Phe-Arg-Trp (5-8) | >100000 | >100000 | >100000 | 10100±330 85%@100μM |
>100000 |
The indicated errors represent the standard error of the mean determined from at least three independent experiments. >100,000 indicates that agonist or antagonist activity was not observed for these compounds at up to 100μM concentrations. A percentage value indicates that some stimulatory agonist pharmacology resulted at up to 100 μM concentrations, but the maximal stimulation levels were less then the 100% control level of NDP-MSH.