. Author manuscript; available in PMC: 2014 Mar 5.

Published in final edited form as: Bioorg Med Chem Lett. 2013 Apr 3;23(11):3434–3437. doi: 10.1016/j.bmcl.2013.03.065

Table 2.

Bioactivities of the designed peptide analogs

No.	hDOR^a [³H]DPDPE^b	rMOR^a [³H]DAMGO^c	[³⁵S]GTP-γ-S binding				IC₅₀^e (nM)
			hDOR^d		rMOR^d		IC₅₀^e (nM)

	K_i (nM)^f	K_i(nM)^f	EC₅₀^g (nM)	E_max^h (%)	EC₅₀ (nM)^g	E_max(%)^h	MVD (δ)	GPI/LMMP (μ)
13ⁱ	1.1	0.90	60	140	60	140	33 ± 6	110 ± 50
13^j	0.99	0.97	60	140	69	140	35 ± 6	42 ± 16
14	12	0.09	37	49	45	43	180 ± 20	950 ± 130
15	2.8	0.43	5.8	22	35	77	22 ± 5	97 ± 18
16	630	260	n.r.		n.r.		7500 ± 700	580 ± 150
17	27	13	5.9	64	0.59	13	9.5 ± 2.9	86 ± 16
18^k	4.0	0.73	46	120	9.1	50	360 ± 170	150 ± 40
19	11	0.35	2.2	84	2.8	31	8.6 ± 1.7	98 ± 24
20	0.26	0.50	0.22	19	1.5	59	16 ± 4	120 ± 20
21	1.8	0.15	0.34	10	0.20	32	3.2 ± 1.3	3.8 ± 0.8
22	4.6	0.54	8.3	7	1.4	31	27 ± 8.1	7.7 ± 2.1
23	0.35	0.17	170	11	380	45	40 ± 5	12 ± 2
24	0.51	0.28	1.1	17	2.2	68	8.8 ± 3.0	67 ± 15
25	0.63	1.5	2.8	27	12	29	12 ± 2	130 ± 60
26	84	64	n.r.		56.	21	510 ± 130	480 ± 910
27	590	130	n.r.		n.r.		1000 ± 200	2100 ± 30
28	0.28	9000	1.7	59	n.r.^l		6.7 ± 3.9	49 ± 16
29	24	1.5	90	33	220	21	120 ± 20	1900 ± 40
Biphalin	2.6 ± 0.4	1.4 ± 0.2	2.5 ± 0.5	27 ± 4	6.0 ± 0.2	25 ± 5	27 ± 2	8.8 ± 0.3
Endomorphin-1	5100 ± 660	4.6 ± 0.2					26 ± 3	11 ± 1
Deltorphin II	1.3	500 ± 40					0.37 ± 0.04	>3000
Dyn A-(1-13)-OH	3.8 ± 0.4	4.0 ± 0.4					6.3 ± 0.9	1.2 ± 0.1

n.r. no response.

Competition analyses were carried out using membrane preparations from transfected HN9.10 cells that constitutively expressed the respective receptor types.

K_d = 0.50 ± 0.1 nM.

K_d = 0.85 ± 0.2 nM.

Expressed from CHO cell.

Concentration at 50% inhibition of muscle concentration at electrically stimulated isolated tissues; these values represent the mean of four tissues within 95% confidence limit.

Competition against radiolabeled ligand, data collected from at least 2 independent experiments in duplicate.

Anti-logarithmic value of the respective EC₅₀.

^h–g

Net total bound/basal binding × 100 ± SEM.

^i–h

Compound 13 is a hydrochloride salt of 13.

^j–i

Effect is not reversed by naloxone.

^k–g

Tested in the free base form.

^l–k

Tested as a trifluoroacetate salt.