Nikiforovich G V, Golbraikh A A, Shenderovich M D, Balodis J
Institute of Organic Synthesis, Latvian SSR Academy of Sciences, Riga.
Int J Pept Protein Res. 1990 Sep;36(3):209-18. doi: 10.1111/j.1399-3011.1990.tb00969.x.
Models of mu- and delta-receptor-bound backbone conformations of enkephalin cyclic analogues containing Phe4 were determined by comparing geometrical similarity among the previously found low-energy backbone structures of [D-Cys2,Cys5]-enkephalinamide, [D-Cys2,D-Cys5]-enkephalinamide, [D-Pen2,L-Pen5]-enkephalin and [D-Pen2,D-Pen5]-enkephalin. The present mu-receptor-bound conformation resembles a beta-I bend in the peptide backbone centred on the Gly3-Phe4 region. Two slightly different models were found for the delta-receptor-bound conformation; both of them are more extended than the mu-receptor-bound conformation and include a gamma-turn (or a gamma-like turn) on the Gly3 residue. Energetically favourable rotamers of Tyr and Phe side chains were also determined for the mu- and delta-conformations. The present models of mu- and delta-conformations share geometrical similarity with the low-energy structures of Leu-enkephalin and the Tyr-D-Lys-Gly-Phe-analogue.
通过比较先前发现的[D-Cys2,Cys5]-脑啡肽酰胺、[D-Cys2,D-Cys5]-脑啡肽酰胺、[D-Pen2,L-Pen5]-脑啡肽和[D-Pen2,D-Pen5]-脑啡肽的低能主链结构之间的几何相似性，确定了含有苯丙氨酸4的脑啡肽环类似物与μ和δ受体结合的主链构象模型。目前与μ受体结合的构象类似于以Gly3-Phe4区域为中心的肽主链中的β-I弯曲。发现了两种略有不同的与δ受体结合的构象模型；它们都比与μ受体结合的构象更伸展，并且在Gly3残基上包含一个γ-转角（或类似γ的转角）。还确定了与μ和δ构象相关的酪氨酸和苯丙氨酸侧链的能量有利旋转异构体。目前的μ和δ构象模型与亮氨酸脑啡肽和酪氨酸-D-赖氨酸-甘氨酸-苯丙氨酸类似物的低能结构具有几何相似性。
