Table 3.
Pharmacology of Beta-hairpin Based Ligands at the Mouse Melanocortin Receptors (Ki=10−pA2).a
| Peptide | Structure | mMC1R | mMC3R | mMC4R | mMC5R | ||
|---|---|---|---|---|---|---|---|
|
| |||||||
| Agonist EC50 (μM) | Antagonist pA2 | Ki(nM) | Antagonist pA2 | Ki(nM) | Agonist EC50 (μM) | ||
|
| |||||||
| 6 | c[Pro-Arg-Phe-Phe-Asn-Ala-Phe-DPro] | 4.5±0.2 | 6.4±0.2 | 400 | 7.7±0.1 | 20 | >100,000 |
| 7 | c[Pro -Arg-Bip -Phe -Asn-Ala-Phe-DPro] | 0.8±0.2 | 6.2±0.1 | 630 | 6.8±0.1 | 160 | >100,000 |
| 8 | c[Pro-Arg-Tic-Phe-Asn-Ala-Phe-DPro] | >100,000 | >100,000 | >100,000 | >100,000 | ||
| 9 | c[Pro-Arg-Phg-Phe-Asn-Ala-Phe-DPro] | 13.6±6.6 | >100,000 | >100,000 | >100,000 | ||
| 10 | c[Pro-Arg-hPhe-Phe-Asn-Ala-Phe-DPro] | 1.5±0.6 | >100,000 | 7.0±0.1 | 100 | >100,000 | |
| 11 | c[Pro-Arg-Anc-Phe-Asn-Ala-Phe-DPro] | 2.5±1.1 | >100,000 | >100,000 | >100,000 | ||
| 12 | c[Pro -Arg-Nal(1′)-Phe-Asn-Ala-Phe-DPro] | 2.5±1.0 | 6.1±0.1 | 790 | 7.8±0.1 | 16 | >100,000 |
| 13 | c[Pro -Arg-Nal(2′)-Phe-Asn-Ala-Phe-DPro] | 8.8±2.6 | 6.0±0.2 | 1,000 | 7.0±0.1 | 100 | >100,000 |
| 14 | c[Pro-Arg-Phe-Bip - Asn-Ala-Phe-DPro] | 0.5±0.3 | >100,000 | 6.8±0.2 | 160 | >100,000 | |
| 15 | c[Pro-Arg-Phe-Tic-Asn-Ala-Phe-DPro] | 3.9±1.0 | >100,000 | >100,000 | >100,000 | ||
| 16 | c[Pro-Arg-Phe-Phg-Asn-Ala-Phe-DPro] | 21.0±9.7 | >100,000 | 5.9±0.1 | 1,300 | >100,000 | |
| 17 | c[Pro-Arg-Phe-hPhe-Asn-Ala-Phe-DPro] | 20.3±8.0 | >100,000 | 8.2±0.1 | 6.3 | >100,000 | |
| 18 | c[Pro-Arg-Phe-Anc-Asn-Ala-Phe-DPro] | 12.1±3.7 | >100,000 | >100,000 | 28±4 | ||
| 19 | c[Pro -Arg-Phe-Nal(1′) - Asn-Ala-Phe-DPro] | 12.7±3.8 | 5.6±0.1 | 2,500 | 7.8±0.2 | 16 | >100,000 |
| 20 | c[Pro -Arg-Phe-Nal(2′) - Asn-Ala-Phe-DPro] | 19.6±6.4 | >100,000 | 7.2±0.1 | 63 | >100,000 | |
| 21 | c[Pro-Arg-Phe-Phe-Gly-Ala-Phe-DPro] | 50% at 100μM | 7.6±0.5 | 25 | 8.4±0.1 | 4.0 | >100,000 |
| 22 | c[Pro-Arg-Phe-Phe-Dap-Ala-Phe-DPro] | 75% at 100μM | 6.9±0.1 | 130 | 9.1±0.1 | 0.79 | >100,000 |
| 23 | c[Pro-Arg-Phe-Phe-Dab-Ala-Phe-DPro] | 50% at 100μM | 7.0±0.1 | 100 | 8.4±0.2 | 4.0 | >100,000 |
| 24 | c[Pro-Arg-Phe-Phe-Orn-Ala-Phe-DPro] | 30% at 10μM | 6.8±0.1 | 160 | 8.3±0.1 | 5.0 | >100,000 |
| 25 | c[Pro-Arg-Phe-Phe-Lys-Ala-Phe-DPro] | >100,000 | 7.0±0.1 | 100 | 8.3±0.3 | 5.0 | >100,000 |
| 26 | c[Pro-Arg-Phe-Phe-Arg-Ala-Phe-DPro] | >100,000 | 6.7±0.2 | 200 | 8.4±0.4 | 4.0 | >100,000 |
a
The indicated errors represent the standard error of the mean determined from at least three independent experiments. The antagonistic pA2 values were determined using the Schild analysis and the antagonist MTII. >100,000 indicates that the compound was examined but lacked agonist or antagonist properties at up to 100 μM concentrations. A percentage denotes the percent maximal stimulatory response observed at 100 μM concentrations but not enough stimulation was observed to determine an EC50 value.