Balalaie Saeed, Malakoutikhah Morteza, Teixidó Meritxell, Fathi Vavsari Vaezeh, Giralt Ernest, Haghighatnia Yaghoub, Hamdan Fatima, Arabanian Armin
Peptide Chemistry Research Center, K. N. Toosi University of Technology, Tehran, Iran.
Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran.
Iran J Pharm Res. 2019 Summer;18(3):1277-1287. doi: 10.22037/ijpr.2019.14712.12602.
An efficient approach for the synthesis of norbuprenorphin derivatives through coupling of enkephalins and norbuprenorphine intermediates is described. Norbuprenorphine derivative was synthesized from thebaine and then, its reaction with succinic acid and phthalic acid was also studied. Meanwhile, the synthesis of enkephalins was done using solid phase peptide synthesis approach. Furthermore, after cleavage of the peptide from the surface of the resin, the coupling of enkephalins with norbuprenorphine derivative was done using TBTU as a coupling reagent then the derivatives were purified using preparative high-pressure liquid chromatography and their structures were confirmed using high-resolution mass spectrometry data. Later, their permeability across membranes was investigated. After PAMPA studies, it was found that the permeability of all norbuprenorphin-enkephalin derivatives was increased; however, succinic and phthalic acid derivatives showed higher permeability than norbuprenorphine-Leu-enkephalin.
描述了一种通过脑啡肽与去甲丁丙诺啡中间体偶联合成去甲丁丙诺啡衍生物的有效方法。去甲丁丙诺啡衍生物由蒂巴因合成，然后研究了其与琥珀酸和邻苯二甲酸的反应。同时，采用固相肽合成方法合成脑啡肽。此外，从树脂表面切割肽后，使用TBTU作为偶联试剂将脑啡肽与去甲丁丙诺啡衍生物偶联，然后使用制备型高压液相色谱法纯化衍生物，并使用高分辨率质谱数据确认其结构。随后，研究了它们对膜的通透性。在平行人工膜渗透实验（PAMPA）研究后发现，所有去甲丁丙诺啡-脑啡肽衍生物的通透性均有所增加；然而，琥珀酸和邻苯二甲酸衍生物的通透性高于去甲丁丙诺啡-亮氨酸-脑啡肽。
