van Wijk G M, Hostetler K Y, Suurmeijer C N, van den Bosch H
Center for Biomembranes and Lipid Enzymology, University of Utrecht, Netherlands.
Biochim Biophys Acta. 1992 Nov 11;1165(1):45-52. doi: 10.1016/0005-2760(92)90074-6.
Phospholipid conjugates of antiretroviral nucleoside analogs have been proposed to have several advantageous features when compared to the parent drugs (Hostetler, K.Y. et al. (1990) J. Biol. Chem. 265, 6112-6117). Here we report on the synthesis of one such type of lipid conjugates, i.e., nucleosides diphosphate diacylglycerols. The syntheses of 3'-azido-3'-deoxythymidine diphosphate diacylglycerol, 3'-deoxythymidine diphosphate diacylglycerol and 2',3'-dideoxycytidine diphosphate diacylglycerol (with different acyl chains) were performed starting from phosphatidic acid and the antiviral nucleoside. A high-performance liquid chromatography procedure for a single step purification of the compounds is presented. The compounds were characterized biochemically, using rat liver enzymes and chemically by phosphorus, fatty acid, ultraviolet, IR and 1H-NMR analyses. Preliminary data on the behaviour in aqueous solution of some of the compounds are presented.
与母体药物相比，抗逆转录病毒核苷类似物的磷脂缀合物已被认为具有若干有利特性（Hostetler，K.Y.等人（1990年）《生物化学杂志》265卷，6112 - 6117页）。在此，我们报告一种此类脂质缀合物即核苷二磷酸二酰甘油的合成。从磷脂酸和抗病毒核苷开始，进行了3'-叠氮基-3'-脱氧胸苷二磷酸二酰甘油、3'-脱氧胸苷二磷酸二酰甘油和2',3'-二脱氧胞苷二磷酸二酰甘油（具有不同酰基链）的合成。给出了用于一步纯化这些化合物的高效液相色谱方法。通过使用大鼠肝脏酶进行生物化学表征，并通过磷、脂肪酸、紫外、红外和1H - NMR分析进行化学表征。给出了一些化合物在水溶液中行为的初步数据。
