Table 1. Agonist versus Antagonist Functional Bioactivities of Modified Tetrapeptides 1–5 at the Human Melanocortin Receptors in Comparison with MT-II^a as a Cyclic Lactam Analogue of α-MSH^b.

		hMC1R				hMC3R				hMC4R				hMC5R
peptide	sequence	IC50 (nM)	%BE	EC50 (nM)	Act%	IC50 (nM)	%BE	EC50 (nM)	Act%	IC50 (nM)	%BE	EC50 (nM)	Act%	IC50 (nM)	%BE	EC50 (nM)	Act%
1	Ac-Aia-d-Phe-Arg-Trp-NH2	1352	50	NA	0	NB		52	20	447	50	0.3	51	636	80	NA	0
2	Ac-Aia-p F-d-Phe-Arg-Trp-NH2	258	40	226	50	5000	50	NA	0	6.5	80	13	100	167	80	4112	50
3	Ac-Aia-p Br-d-Phe-Arg-Trp-NH2	300	80	700	100	100	100	2435	50	200	100	0.3	80	70.3	100	NA	0
4	Ac-Aba-d-Phe-Arg-Trp-NH2	594	80	1000	70	>2000	59	2000	40	220	80	227	80	37.3	75	NA	0
5	Ac-Ata-d-Phe-Arg-Trp-NH2	4540	60	750	100	1000	55	55	20	200	80	203	80	137	70	NA	0
MT-II	Ac-N le-c [Asp-His-d-Phe-Arg-Trp-Lys]-NH2	1 ± 0.1	100	1.02 ± 0.4	100	2.0 ± 0.1	100	5.1 ± 0.3	100	2.3 ± 0.85	100	2.1 ± 0.6	100	4.2 ± 1.3	100	5.7 ± 2.2	100

^aMT-II = Ac-Nle-c[Asp-His-d-Phe-Arg-Trp-Lys]-NH₂.

^bIC₅₀ = concentration of peptide at 50% specific binding (N = 4). NB = 0% of ¹²⁵I-NDP-α-MSH displacement observed at 10 μM. %BE (binding efficiency) = maximal % of ¹²⁵I-NDP-α-MSH displacement observed at 10 μM. EC₅₀ = Effective concentration of peptide that was able to generate 50% maximal intracellular cAMP accumulation (N = 4). Act% = % of cAMP produced at 10 μM ligand concentration, in relation to MT-II. NA = 0% cAMP accumulation observed at 10 μM. The peptides were tested at a range of concentration from 10^–10 to 10^–5 M.