Issue 20, 2022

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

Abstract

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 the halotolerant 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 a study case, we obtained the highest space–time yield (5.5 g L−1 h−1) 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.

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

Supplementary files

Article information

Article type
Paper
Submitted
19 Apr 2022
Accepted
08 Aug 2022
First published
08 Aug 2022
This article is Open Access
Creative Commons BY-NC license

Catal. Sci. Technol., 2022,12, 6231-6238

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

A. I. Benítez-Mateos, C. Klein, D. Roura Padrosa and F. Paradisi, Catal. Sci. Technol., 2022, 12, 6231 DOI: 10.1039/D2CY00751G

This article is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported Licence. You can use material from this article in other publications, without requesting further permission from the RSC, provided that the correct acknowledgement is given and it is not used for commercial purposes.

To request permission to reproduce material from this article in a commercial publication, please go to the Copyright Clearance Center request page.

If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given.

If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party commercial publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page.

Read more about how to correctly acknowledge RSC content.

Social activity

Spotlight

Advertisements