Nikiforovich G V, Hruby V J, Prakash O, Gehrig C A
Department of Chemistry, University of Arizona, Tucson 85721.
Biopolymers. 1991 Jul;31(8):941-55. doi: 10.1002/bip.360310804.
The conformational possibilities of three different delta-selective opioid peptides, which are DPDPE (Tyr-D-Pen-Gly-Phe-D-Pen), DCFPE (Tyr-D-Cys-Phe-D-Pen), and DRE (Tyr-D-Met-Phe-His-Leu-Met-Asp-NH2, dermenkephalin), were explored using energy calculations. Sets of low-energy conformers were obtained for each of these peptides. The sets consisted of 61 structures for DPDPE, 32 for DCFPE, and 38 for DRE, including various types of rotamers of the Tyr and Phe side-chain groups. Comparison of the geometrical shapes of the conformers was performed for these sets using topographical considerations, i.e., examination of the mutual spatial arrangement of the N-terminal alpha-amino group, and of the Tyr and Phe side-chain groups. The results obtained suggest a model for the delta-receptor-bound conformer(s) for opioid peptides. The model suggests the placement of the Phe side chain in a definite position in space corresponding to the g- rotamer of Phe for peptides containing Phe4 and to the t rotamer for peptides containing Phe. The position of the Tyr1 side chain cannot be specified so precisely. The proposed model is in a good agreement with the results of biological testing of beta-Me-Phe4-substituted DPDPE analogues that were not considered in the process of model construction.
利用能量计算方法，研究了三种不同的δ-选择性阿片样肽（分别为DPDPE（酪氨酸-D-青霉胺-甘氨酸-苯丙氨酸-D-青霉胺）、DCFPE（酪氨酸-D-半胱氨酸-苯丙氨酸-D-青霉胺）和DRE（酪氨酸-D-蛋氨酸-苯丙氨酸-组氨酸-亮氨酸-蛋氨酸-天冬酰胺，即皮肤脑啡肽））的构象可能性。为每种肽获得了低能量构象体集合。这些集合包括DPDPE的61种结构、DCFPE的32种结构和DRE的38种结构，其中包括酪氨酸和苯丙氨酸侧链基团的各种类型的旋转异构体。使用地形学考虑因素，即检查N端α-氨基以及酪氨酸和苯丙氨酸侧链基团的相互空间排列，对这些集合中的构象体的几何形状进行了比较。所得结果提出了一种阿片样肽与δ-受体结合的构象体模型。该模型表明，对于含有苯丙氨酸4的肽，苯丙氨酸侧链处于空间中对应于苯丙氨酸的g-旋转异构体的确定位置，对于含有苯丙氨酸的肽，苯丙氨酸侧链处于t-旋转异构体的位置。酪氨酸1侧链的位置不能如此精确地确定。所提出的模型与在模型构建过程中未考虑的β-甲基-苯丙氨酸4取代的DPDPE类似物的生物学测试结果高度一致。
