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Immobilized enzyme reactors based on nucleoside phosphorylases and 2'-deoxyribosyltransferase for the in-flow synthesis of pharmaceutically relevant nucleoside analogues
Bioresource Technology ( IF 11.4 ) Pub Date : 2020-03-26 , DOI: 10.1016/j.biortech.2020.123258
Francesca Rinaldi , Jesús Fernández-Lucas , Diego de la Fuente , Changping Zheng , Teodora Bavaro , Benjamin Peters , Gabriella Massolini , Francesca Annunziata , Paola Conti , Isabel de la Mata , Marco Terreni , Enrica Calleri

In this work, a mono- and a bi-enzymatic analytical immobilized enzyme reactors (IMERs) were developed as prototypes for biosynthetic purposes and their performances in the in-flow synthesis of nucleoside analogues of pharmaceutical interest were evaluated. Two biocatalytic routes based on nucleoside 2'-deoxyribosyltransferase from Lactobacillus reuteri (LrNDT) and uridine phosphorylase from Clostridium perfrigens (CpUP)/purine nucleoside phosphorylase from Aeromonas hydrophila (AhPNP) were investigated in the synthesis of 2'-deoxy, 2',3'-dideoxy and arabinonucleoside derivatives. LrNDT-IMER catalyzed the synthesis of 5-fluoro-2'-deoxyuridine and 5-iodo-2'-deoxyuridine in 65-59% conversion yield, while CpUP/AhPNP-IMER provided the best results for the preparation of arabinosyladenine (60% conversion yield).

Both IMERs proved to be promising alternatives to chemical routes for the synthesis of nucleoside analogues. The developed in-flow system represents a powerful tool for the fast production on analytical scale of nucleosides for preliminary biological tests.



中文翻译:

基于核苷磷酸化酶和2'-脱氧核糖基转移酶的固定化酶反应器,用于药物相关核苷类似物的流式合成

在这项工作中,开发了单酶和双酶分析固定化酶反应器(IMERs)作为用于生物合成目的的原型,并评估了它们在流式合成药物性核苷类似物中的性能。研究了两种基于罗伊氏乳杆菌核苷2'-脱氧核糖基转移酶(Lr NDT)和来自产气荚膜梭菌的尿苷磷酸化酶Cp UP)/嗜水气单胞菌的嘌呤核苷磷酸化酶(Ah PNP)的生物催化路线。',3'-二脱氧和阿拉伯核苷衍生物。rNDT-IMER以65-59%的转化率催化了5-氟-2'-脱氧尿苷和5-碘-2'-脱氧尿苷的合成,而Cp UP / Ah PNP-IMER为制备阿拉伯糖基腺嘌呤提供了最好的结果( 60%的转化率)。

事实证明,两种IMER都是合成核苷类似物的化学途径的有前途的替代方法。先进的流入系统代表了一种强大的工具,可以快速生产初步分析的核苷分析规模。

更新日期:2020-03-27
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