Grogan, Gideon James orcid.org/0000-0003-1383-7056, Salihovic, Admir, Ascham, Alexander et al. (6 more authors) (2024) Gram-Scale Enzymatic Synthesis of 2ʹ-Deoxyribonucleoside Analogues Using Nucleoside Transglycosylase-2. Chemical Science. ISSN 2041-6539
Abstract
Nucleosides are pervasive building blocks that are found throughout nature and used extensively in medicinal chemistry and biotechnology. However, the preparation of base-modified analogues using conventional synthetic methodology poses challenges in scale-up and purification. In this work, an integrated approach involving structural analysis, screening and reaction optimization, is established to prepare 2'-deoxyribonucleoside analogues catalysed by the Type II nucleoside 2'-deoxyribosyltransferase from Lactobacillus leichmannii (LlNDT-2). Structural analysis in combination with substrate profiling, identified the constraints on pyrimidine and purine acceptor bases by LlNDT2. A solvent screen identifies pure water as a suitable solvent for the preparation of high value purine and pyrimidine 2'-deoxyribonucleoside analogues on a gram scale under optimized reaction conditions. This approach provides the basis to establish a convergent, step- efficient chemoenzymatic platform for the preparation of high value 2'-deoxyribonucleosides.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Dates: |
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Institution: | The University of York |
Academic Units: | The University of York > Faculty of Sciences (York) > Chemistry (York) |
Depositing User: | Pure (York) |
Date Deposited: | 02 Sep 2024 13:10 |
Last Modified: | 02 Apr 2025 23:28 |
Published Version: | https://doi.org/10.1039/D4SC04938A |
Status: | Published online |
Refereed: | Yes |
Identification Number: | 10.1039/D4SC04938A |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:216726 |