Castiglione-Morelli M A, Lelj F, Pastore A, Salvadori S, Tancredi T, Tomatis R, Trivellone E, Temussi P A
Dipartimento di Chimica, Università di Napoli, Italy.
J Med Chem. 1987 Nov;30(11):2067-73. doi: 10.1021/jm00394a023.
The structure-activity relationship of several mu selective opioid peptides has been evaluated on the basis of both experimental and theoretical approaches. The conformations of Tyr-D-Ala-Phe-Gly-NH2, the tetrapeptide N-fragment of dermorphin, and two analogues have been studied in solution by 1H NMR spectroscopy. The physicochemical environment inside the receptor has been simulated by complexing the peptides with a crown ether and dissolving the complexes in chloroform. The family of conformations derived from the NMR data possesses most of the features previously proposed for mu agonists and is fully consistent with an original model of the mu receptor based on the structures of many rigid opiates. As a simple test of this model, the synthesis of a linear peptide with significant mu activity in spite of the absence of Tyr1 is reported.
基于实验和理论方法，对几种μ选择性阿片肽的构效关系进行了评估。通过¹H NMR光谱研究了强啡肽的四肽N片段Tyr-D-Ala-Phe-Gly-NH₂及其两种类似物在溶液中的构象。通过将肽与冠醚络合并将络合物溶解在氯仿中来模拟受体内部的物理化学环境。从NMR数据得出的构象家族具有先前为μ激动剂提出的大多数特征，并且与基于许多刚性阿片类药物结构的μ受体原始模型完全一致。作为对该模型的一个简单测试，报道了一种尽管没有Tyr1但仍具有显著μ活性的线性肽的合成。
