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. 2007 Jun 14;50(12):2753-66.
doi: 10.1021/jm061238m. Epub 2007 May 12.

Bifunctional [2',6'-dimethyl-L-tyrosine1]endomorphin-2 analogues substituted at position 3 with alkylated phenylalanine derivatives yield potent mixed mu-agonist/delta-antagonist and dual mu-agonist/delta-agonist opioid ligands

Tingyou Li  1 , Kimitaka Shiotani, Anna Miyazaki, Yuko Tsuda, Akihiro Ambo, Yusuke Sasaki, Yunden Jinsmaa, Ewa Marczak, Sharon D Bryant, Lawrence H Lazarus, Yoshio Okada
Affiliations

Bifunctional [2',6'-dimethyl-L-tyrosine1]endomorphin-2 analogues substituted at position 3 with alkylated phenylalanine derivatives yield potent mixed mu-agonist/delta-antagonist and dual mu-agonist/delta-agonist opioid ligands

Tingyou Li et al. J Med Chem. .

Abstract

Endomorphin-2 (H-Tyr-Pro-Phe-Phe-NH2) and [Dmt1]EM-2 (Dmt = 2',6'-dimethyl-l-tyrosine) analogues, containing alkylated Phe3 derivatives, 2'-monomethyl (2, 2'), 3',5'- and 2',6'-dimethyl (3, 3', and 4', respectively), 2',4',6'-trimethyl (6, 6'), 2'-ethyl-6'-methyl (7, 7'), and 2'-isopropyl-6'-methyl (8, 8') groups or Dmt (5, 5'), had the following characteristics: (i) [Xaa3]EM-2 analogues exhibited improved mu- and delta-opioid receptor affinities. The latter, however, were inconsequential (Kidelta = 491-3451 nM). (ii) [Dmt1,Xaa3]EM-2 analogues enhanced mu- and delta-opioid receptor affinities (Kimu = 0.069-0.32 nM; Kidelta = 1.83-99.8 nM) without kappa-opioid receptor interaction. (iii) There were elevated mu-bioactivity (IC50 = 0.12-14.4 nM) and abolished delta-agonism (IC50 > 10 muM in 2', 3', 4', 5', 6'), although 4' and 6' demonstrated a potent mixed mu-agonism/delta-antagonism (for 4', IC50mu = 0.12 and pA2 = 8.15; for 6', IC50mu = 0.21 nM and pA2 = 9.05) and 7' was a dual mu-agonist/delta-agonist (IC50mu = 0.17 nM; IC50delta = 0.51 nM).

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Figures

Figure 1
Figure 1
Schematic Structure of Endomorphin-2 with Alkylation Sites (R1–R6) on Tyr1 and Phe3.
See this image and copyright information in PMC

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References

    1. Zadina JE, Hackler L, Ge LJ, Kastin AJ. A Potent and selective endogenous agonist for the mu-opiate receptor. Nature. 1997;386:499–502. - PubMed
    1. Wilson AM, Soignier RD, Zadina JE, Kastin AJ, Nores WL, Olson RD, Olson GA. Dissociation of analgesic and rewarding effects of endomorphin-1 in rats. Peptides. 2000;21:1871–1874. - PubMed
    1. Carrigan KA, Nelson CJ, Lysle DT. Endomorphin-1 induces antinociception without immunomodulatory effects in the rat. Psychopharmacology. 2000;151:299–305. - PubMed
    1. Harrison LM, Kastin AJ, Zadina JE. Differential effects of endomorphin-1,endomorphin-2, and Tyr-W-MIF-1 on activation of G-proteins in SH-SY5Y human neuroblastoma membranes. Peptides. 1998;19:749–753. - PubMed
    1. Kakizawa K, Shimohira I, Sakurada S, Fujimura T, Murayama K, Ueda H. Parallel stimulations of in vitro and in situ [35S]GTPγS binding by endomorphin 1 and DAMGO in mouse brains. Peptides. 1998;19:755–758. - PubMed

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