A novel thymidine phosphorylase to synthesize (halogenated) anticancer and antiviral nucleoside drugs in continuous flow

Benitez-Mateos, Ana I; Klein, Calvin; Roura Padrosa, David; Paradisi, Francesca (2022). A novel thymidine phosphorylase to synthesize (halogenated) anticancer and antiviral nucleoside drugs in continuous flow. Catalysis science & technology, 12(20), pp. 6231-6238. Royal Society of Chemistry 10.1039/D2CY00751G

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Four pharmaceutically relevant nucleoside analogues (5-fluoro-2’-deoxyuridine, 5-chloro-2’-deoxyuridine, 5-bromo-2’-deoxyuridine, and 5-iodo-2’-deoxyuridine) have been synthesized by using a novel thymidine phosphorylase from H. elongata (HeTP). Following enzyme immobilization on microbeads, the biocatalyst was implemented as a packed-bed reactor for the continuous production of halogenated nucleosides, achieving up to 90% conversion at the 10 mM scale with 30 min residence time. Taking the synthesis of Floxuridine (5-fluoro-2’-deoxyuridine) as study case, we obtained the highest space-time yield (5.5 g/L/h) reported to date. In addition, bioinformatic tools such as MD analysis and CapiPy have contributed to shine light on the catalytic performance of HeTP as well as its immobilization, respectively.

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