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.
Original language | English |
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Pages (from-to) | 15399-15407 |
Number of pages | 9 |
Journal | Chemical Science |
Volume | 15 |
Issue number | 37 |
Early online date | 27 Aug 2024 |
DOIs | |
Publication status | Published - 7 Oct 2024 |
Keywords
- nucleosides
- base-modified analogues
- 2′-deoxyribonucleosides
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Data for: ''Gram-scale enzymatic synthesis of 2′-deoxyribonucleoside analogues using nucleoside transglycosylase-2''
Salihovic, A. (Creator) & Burley, G. (Supervisor), University of Strathclyde, 4 Sept 2024
DOI: 10.15129/f4781c2d-fa2f-4b38-bba6-401d18ff5cd0
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