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

Table 6

Opioid receptor-binding affinity and biological activities of opioid peptide analogs containing Dmp at position 1.

Peptide	Receptor binding affinity, 𝐾𝑖±S. E. (nM)				GPI (μ)	MVD (𝛿)
	μ ^a	𝛿^b	𝛿/μ	μ/𝛿	IC50 (nM)	IC50 (nM)	MVD/GPI	GPI/MVD
Tyr-Gly-Gly-Phe-Leu (ENK)	2.42 ± 0.93	1.43 ± 0.71	—	1.69	103 ± 30	22.2 ± 4.3	—	4.64
[Dmp^1]ENK (32)	5.94 ± 1.45	1.86 ± 0.61	—	3.19	710 ± 69	66.6 ± 12.7	—	10.66
[Dmt^1]ENK^c	0.0068 ± 0.003	0.031 ± 0.011	—	0.22	0.55 ± 0.17	0.17 ± 0.02	—	3.24
[Phe^1]ENK (33)	169 ± 12	73.7 ± 19.5	—	2.29	>10000	>10000	—	—
Deltorphin II (DT)	314 ± 53	0.0226 ± 0.0077	—	13894	5437 ± 812	0.582 ± 0.029	—	9342
[Dmp^1]DT  (34)	156 ± 33	0.329 ± 0.077	—	475	4038 ± 1118	0.272 ± 0.054	—	14835
[D-Dmp^l]DT  (35)	>2178	1394 ± 495	—	—	>10000	662 ± 147	—	—
[Dmt^1]DT  (36)	0.261± 0.060	0.012 ± 0.002	—	21.8	88.4 ± 22.7	0.052 ± 0.007	—	1700
[Phe^1]DT  (37)	>2178	2.68 ± 1.22	—	—	>10000	10.4 ± 1.5	—	—
Tyr-Pro-Phe-Phe-NH2 (EM2)	0.557 ± 0.306	14,070 ± 3346	25260	—	10.5 ± 1.2	317 ± 65	30.2	—
[Dmp^1]EM2 (38)	2.48 ± 1.46	6762 ± 590	2727	—	76.9 ± 20.7	661± 316	8.61	—
[D-Dmp^1]EM2 (39)	40.4 ± 2.6	9714 ± 3820	241	—	1392 ± 221	2329 ± 943	167	—
[Dmt^1]EM2^d	0.15 ± 0.04	—	—	—	0.07± 0.02	1.87 ± 0.61	26.7	—
[Phe^1]EM2 (40)	54.1± 23.4	18,851 ± 10,487	348	—	1073 ± 309	5,199 ± 2,584	4.85	—
Tyr-D-Arg-Phe-βAla-NH2 (YRFB)	0.172 ± 0.025	482 ± 121	2802	—	531± 0.72	116 ± 18	21.8	—
[Dmp^1]YRFB (24)	0.0623 ± 0.0140	2572 ± 947	41284	—	9.88 ± 1.04	188 ± 52	19	—
[D-Dmp^1]YRFB (41)	7.62 ± 1.75	>2823	>370	—	320 ± 30	1474 ± 283	4.6	—
[Dmp^1,3]YRFB (25)	0.0216 ± 0.0062	1688 ± 458	78148	—	2.76 ± 0.56	501 ± 86	18.2	—
[Dmt^1]YRFB^c	0.00205 ± 0.00069	1.13 ± 0.13	551	—	0.034 ± 0.065	0.398 ± 0.085	11.7	—
[Phe^1]YRFB (42)	7.17 ± 1.03	>2823	>393	—	633 ± 89	7143 ± 950	11.2	—

^aVersus [³H]DAMGO. ^bVersus [³H]DT. ^cData cited from [39]. ^dData cited from [29].