2^′, 6^′-Dimethylphenylalanine : A Useful Aromatic Amino Acid Surrogate for Tyr or Phe Residue in Opioid Peptides

Table 4

Receptor-binding affinity of DYN analogs and NOC analogs containing Dmp for opioid receptors and ORLl receptor.

Peptides	IC50 ± SEM (nM)
	ORL1 receptor	Opioid receptor
	[^3H]NOC^a	[^3H]U-69593 (κ)^b	[^3H]DAMGO (𝜇)^c	[^3H]DT (δ)^c	κ/𝜇/δ
DYN(I-13)-NH2	18.8 ± 3.01	0.162 ± 0.049	2.53 ± 0.38	6.49 ± 1.11	1/15.6/40.1
[Dmp^4]DYN (1-13)- NH2 (26)	188 ± 18.2	0.044 ± 0.035	22.4 ± 10.2	931 ± 723	1/509/21159
[Dmp^1]DYN(1-13)-NH2 (27)	6.60 ± 0.952	0056 ± 0026	16.4 ± 2.35	10.1 ± 6.02	1/293/180
[Dmp^1,4]DYN (1-13)- NH2 (28)	51.5 ± 1.62	5.45 ± 1.65	251 ± 56.3	415 ± 185	1/46/76.1
NOC	0.151 ± 0.058	643 ± 218	1540 ± 601	>10000	—
NOC(1-13)-NH2	0.743 ± 0.125	193 ± 54	319 ± 88	>10000	—
[Dmp^4]NOC( 1-13)- NH2 (29)	51.6 ± 12.9	299 ± 63	629 ± 433	>10000	—
[Dmp^1]NOC(1-13)-NH2 (30)	0.814 ± 0.090	38.8 ± 16.7	25.0 ± 6.5	292 ± 61	—
[Dmp^l,4]NOC(1-13)- NH2 (31 )	21.3 ± 3.2	100 ± 29	56.8 ± 12.3	3407 ± 990	—

^aUsing cell membrane expressing human ORL1 receptor in Hek-293 cells. ^bUsing guinea pig brain homogenate.
^cUsing rat brain homogenate.