Department of Pharmaceutical Sciences, University of Milan, via Mangiagalli 25, 20133 Milano, Italy.
Department of Drug Sciences, University of Pavia, viale Taramelli 12, 27100 Pavia, Italy.
Molecules. 2020 Mar 9;25(5):1223. doi: 10.3390/molecules25051223.
The bi-enzymatic synthesis of the antiviral drug vidarabine (arabinosyladenine, ara-A), catalyzed by uridine phosphorylase from (UP) and a purine nucleoside phosphorylase from (PNP), was re-designed under continuous-flow conditions. Glyoxyl-agarose and EziG1 (Opal) were used as immobilization carriers for carrying out this preparative biotransformation. Upon setting-up reaction parameters (substrate concentration and molar ratio, temperature, pressure, residence time), 1 g of vidarabine was obtained in 55% isolated yield and >99% purity by simply running the flow reactor for 1 week and then collecting (by filtration) the nucleoside precipitated out of the exiting flow. Taking into account the substrate specificity of UP and PNP, the results obtained pave the way to the use of the UP/PNP-based bioreactor for the preparation of other purine nucleosides.
抗病毒药物阿昔洛韦（阿拉伯糖基腺嘌呤，ara-A）的双酶合成，由来自 （UP）的尿苷磷酸化酶和来自 （PNP）的嘌呤核苷磷酸化酶催化，在连续流动条件下重新设计。乙二醛琼脂糖和 EziG1（蛋白石）被用作固定化载体，以进行这种制备性生物转化。在设定反应参数（底物浓度和摩尔比、温度、压力、停留时间）后，通过简单地运行流动反应器 1 周，然后收集（通过过滤）从流出物中沉淀出来的核苷，以 55%的分离产率和 >99%的纯度获得 1 克阿昔洛韦。考虑到 UP 和 PNP 的底物特异性，所获得的结果为基于 UP/PNP 的生物反应器用于制备其他嘌呤核苷铺平了道路。
