Doi M, Tanaka M, Ikuma K, Nabae M, Kitamura K, Inoue M, Ishida T
Osaka University of Pharmaceutical Sciences, Japan.
Biochem J. 1988 Apr 15;251(2):581-8. doi: 10.1042/bj2510581.
An investigation on the conformations of highly receptor-selective opioid peptides was carried out to gain further understanding of the structure-activity relationship of endogenous enkephalins. The preferred conformations of a highly mu-selective [Val4]morphiceptin and a highly delta-selective delta-kephalin have been probed by 1H n.m.r. solvent-, concentration- and temperature-dependences of amide protons to take the folded conformations stabilized by an intramolecular hydrogen bond and the anti-parallely extended dimeric structures respectively. Their possible stereo-conformations were proposed, based on the analyses of the vicinal coupling constants (JHNC alpha H). The conformational difference between the mu- and delta-selective opioid peptides was further ascertained by the c.d. measurements. The c.d. spectra of the mu-selective peptides show negative bands in the range of 210-230 nm, while those of the delta-selective ones show the opposite positive bands. A correlation between c.d. spectra and receptor-selectivity was possible.
为了进一步了解内源性脑啡肽的构效关系，对高受体选择性阿片肽的构象进行了研究。通过1H核磁共振对高度μ选择性的[Val4]吗啡肽和高度δ选择性的δ-脑啡肽的优选构象进行了探测，酰胺质子的溶剂、浓度和温度依赖性分别呈现出由分子内氢键稳定的折叠构象和反平行延伸的二聚体结构。基于邻位耦合常数（JHNCαH）的分析，提出了它们可能的立体构象。通过圆二色性测量进一步确定了μ和δ选择性阿片肽之间的构象差异。μ选择性肽的圆二色光谱在210-230nm范围内显示负带，而δ选择性肽的圆二色光谱显示相反的正带。圆二色光谱与受体选择性之间可能存在相关性。
