Potent μ-Opioid Receptor Agonists from Cyclic Peptides Tyr-c[d-Lys-Xxx-Tyr-Gly]: Synthesis, Biological, and Structural Evaluation
作者： Yangmei Li , Margret Cazares , Jinhua Wu , Richard A. Houghten , Laurence Toll
DOI: 10.1021/ACS.JMEDCHEM.5B01899
关键词: Ligand (biochemistry) 、 Opioid receptor 、 Selectivity 、 Chemistry 、 Receptor 、 Combinatorial chemistry 、 Structure–activity relationship 、 Biological activity 、 Cyclic peptide 、 Agonist
摘要: To optimize the structure of a μ-opioid receptor ligand, analogs H-Tyr-c[D-Lys-Xxx-Tyr-Gly] were synthesized and their biological activity was tested. The analog containing Phe(3) identified as not only exhibiting binding affinity 14-fold higher than original hit but also producing agonist 3-fold more potent morphine. NMR study suggested that trans conformation at D-Lys(2)-Xxx(3) is crucial for these cyclic peptides to maintain high affinity, selectivity, functional toward receptor.
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