Table 1.

Agonist EC₅₀ (nM) and antagonist pA₂ pharmacology of the modified peptides at the mouse melanocortin receptors.

Ligand					mMC1R	Fold	mMC3R	Fold	mMC4R	Fold	mMC5R	Fold
	R1	R2	R3	R4	EC50 (nM)	Diff	EC50 (nM)	Diff	EC50 (nM)	Diff	EC50 (nM)	Diff
NDP-MSH					0.05±0.02		0.23±0.03		0.20±0.02		0.28±0.04
Control Peptide 1 (AMW3-130)					0.30±0.18		1.70±0.33		0.17±0.04		1.45±0.63
2	His	DPhe	Arg	Trp	2.4±0.5	1.0	324±44	1.0	190±20	1.0	46±11	1.0
3	Ala	DPhe	Arg	Trp	52±20	22	4020±745	12	705±100	-	690±140	15
4	Phe	DPhe	Arg	Trp	1.94±0.55	-	4500±1950	14	290±22	-	415±65	9
5	Pro	DPhe	Arg	Trp	32±17	13	1900±810	6	240±6	-	270±135	6
6	His	Pro	Arg	Trp	5000±2900	2080	10350±3800	32	5400±1040	28	1100±530	24
7	His	Ala	Arg	Trp	12500±9900	5208	7720±3900	24	20100±4200	106	7700±2200	167
8	His	DNal(1′)	Arg	Trp	7.4±0.9	-	190±40	-	130±24	-	205±100	-
9	His	DNal(2′)	Arg	Trp	8.7±1.3	-	Antagonist pA2=7.6±0.2 partial agonist (20% maximal efficacy)	(9)	190±40	-	46±7	-
10	His	(pI)DPhe	Arg	Trp	0.50±0.08	(4)	49±8	(6)	20±3	(9)	9.8±4.7	(4)
11	His	DBip	Arg	Trp	1.1±0.8	-	Antagonist pA2=9.9±0.4 partial agonist (10% maximal efficacy)	(2492)	760±220	-	87±16	-
12	His	DPhe	Ala	Trp	19±7	8	8070±2400	25	1300±340	6	850±74	18
13	His	DPhe	Lys	Trp	30±14	12	2540±360	7	420±63	-	460±60	10
14	His	DPhe	hArg	Trp	15±3.9	6	1830±490	5	965±442	5	350±145	7
15	His	DPhe	Pro	Trp	16±2	6	7120±3510	22	1270±280	7	630±144	14
16	His	DPhe	Arg	Ala	80±20	33	2230±610	7	210±57	-	125±41	-
17	His	DPhe	Arg	Nal(2′)	6.2±1.0	-	200±13	-	220±72	-	52±19	-
18	His	DPhe	Arg	DNal(2′)	14±4	5	180±12	-	50±9	(4)	29±20	-
19	His	DPhe	Arg	Bip	20±6	8	230±30	-	980±170	5	830±215	18

The indicated errors represent the standard error of the mean determined from at least three independent experiments.

The potency of the antagonist was determined by using the equation pA2 = −Log Ki where Ki is estimted as the ligand potency in nM.

A parentheses () indicates that an increase in potency has resulted.

Changes less than 3-fold are considered to be within the inherent experimental assay error.