Piestrzeniewicz Mariola Katarzyna, Fichna Jakub, Janecka Anna
Laboratory of Biomolecular Chemistry, Institute of Biomedicinal Chemistry, Medical University of łódź, 6/8Mazowiecka St., 92-215 łódź, Poland.
Postepy Biochem. 2006;52(3):313-9.
Opioid receptors (micro, delta, and kappa) belong to a large family of G protein-coupled receptors and play an important physiological role. Stimulation of these receptors triggers analgesic effects and affects the function of gastrointestinal tract. The discovery of opioid peptides, which are endogenous ligands of opioid receptors, including delta-selective enkephalins, kappa-selective dynorphins, and micro-selective endomorphins, initiated their structure-activity relationship studies. For the last 30 years, hundreds of analogs of opioid peptides have been synthesized in an effort to obtain the compounds more active, selective, and resistant to biodegradation than the endogenous ligands. Different unnatural amino acids, as well as cyclisation procedures, leading to conformationaly restricted analogs, were employed. All these modifications resulted in obtaining very selective agonists and antagonists with high affinity at micro-, dlta-, and kappa-opioid receptors, which are extremely useful tools in further studies on the pharmacology of opioid receptors in a mammalian organism.
阿片受体（μ、δ和κ）属于G蛋白偶联受体大家族，发挥着重要的生理作用。刺激这些受体会引发镇痛作用，并影响胃肠道功能。阿片肽是阿片受体的内源性配体，包括δ选择性脑啡肽、κ选择性强啡肽和μ选择性内吗啡肽，它们的发现开启了其构效关系研究。在过去30年里，人们合成了数百种阿片肽类似物，试图获得比内源性配体更具活性、选择性且抗生物降解的化合物。使用了不同的非天然氨基酸以及环化程序，以得到构象受限的类似物。所有这些修饰都导致获得了对μ、δ和κ阿片受体具有高亲和力的非常选择性的激动剂和拮抗剂，它们是进一步研究哺乳动物机体中阿片受体药理学的极其有用的工具。
