Department of Biomolecular Chemistry, Faculty of Medicine, Medical University of Lodz, Mazowiecka 6/8, 92-215 Lodz, Poland; Department of Gastroenterological Surgery, Tenth People's Hospital of Shanghai, School of Medicine, Tongji University, Shanghai, China.
Bioorg Med Chem Lett. 2013 Dec 15;23(24):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.
我们报告了一种新型糖基化类似物的合成和药理学特征，该类似物是一种强效和选择性的内源性 μ 阿片受体（MOP）激动剂，内吗啡肽-2（Tyr-Pro-Phe-Phe-NH2，EM-2）的类似物，通过在酪氨酸残基的位置 3 引入具有葡萄糖部分的方法获得，该葡萄糖部分通过β-糖苷键连接到酚官能团上。新型糖基化类似物的改善的血脑屏障通透性和增强的镇痛作用表明，它可能是设计强效镇痛药的有前途的模板。此外，所述方法学对于增加阿片肽向 CNS 的生物利用度和递送可能是有用的。
