Fichna Jakub, Janecka Anna, Bailly Laetitia, Marsais Francis, Costentin Jean, do Rego Jean-Claude
Laboratory of Biomolecular Chemistry, Medical University of Lodz, Lodz, Poland.
Chem Biol Drug Des. 2006 Sep;68(3):173-5. doi: 10.1111/j.1747-0285.2006.00425.x.
Endomorphins, endogenous mu-opioid receptor ligands, have been shown to exert antinociceptive, antidepressant, anxiolytic, and neuromodulatory effects, as well as to influence cardiovascular, respiratory, and gastrointestinal systems. In the present study, we designed and synthesized a series of tetrapeptides and tripeptides (amides and peptide acids) of similar to endomorphins structure, but with low mu-opioid receptor affinity, and tested them as possible inhibitors of endomorphin-degrading enzymes. The obtained results indicate that the tripeptides Tyr-Pro-Ala-NH2 and Tyr-Pro-Ala-OH, which do not bind to the mu-opioid receptors, are potent inhibitors of endomorphin-degrading enzymes in the rat brain. We suggest that the in vivo administration of these novel analogs may enhance physiological effects of endogenous endomorphins by decreasing the rate of their enzymatic cleavage.
内吗啡肽作为内源性μ-阿片受体配体，已被证明具有抗伤害感受、抗抑郁、抗焦虑和神经调节作用，还能影响心血管、呼吸和胃肠道系统。在本研究中，我们设计并合成了一系列结构与内吗啡肽相似但对μ-阿片受体亲和力较低的四肽和三肽（酰胺和肽酸），并将它们作为内吗啡肽降解酶的潜在抑制剂进行测试。所得结果表明，不与μ-阿片受体结合的三肽酪氨酸-脯氨酸-丙氨酸-NH2和酪氨酸-脯氨酸-丙氨酸-OH是大鼠脑内内吗啡肽降解酶的有效抑制剂。我们认为，体内给予这些新型类似物可能通过降低内源性内吗啡肽的酶切速率来增强其生理效应。
