Novel glycosylated endomorphin-2 analog produces potent centrally-mediated antinociception in mice after peripheral administration.
Fichna J, Mazur M, Grzywacz D, Kamysz W, Perlikowska R, Piekielna J, Sobczak M, Sałaga M, Toth G, Janecka A, Chen C, Olczak J., Bioorg Med Chem Lett., 2013, 23, 6673-6. doi: 10.1016/j.bmcl.2013.10.041. Epub 2013 Oct 30.
We report the synthesis and pharmacological characterization of a novel glycosylated analog of a potent and selective endogenous μ-opioid receptor (MOP) agonist, endomorphin-2 (Tyr-Pro-Phe-Phe-NH2, EM-2), obtained by the introduction in position 3 of the tyrosine residue possessing the glucose moiety attached to the phenolic function via a β-glycosidic bond. The improved blood-brain barrier permeability and enhanced antinociceptive effect of the novel glycosylated analog suggest that it may be a promising template for design of potent analgesics. Furthermore, the described methodology may be useful for increasing the bioavailability and delivery of opioid peptides to the CNS.
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Keyword: Peptide Inhibitors
