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Gram-scale enzymatic synthesis of 2'-deoxyribonucleoside analogues using nucleoside transglycosylase-2.


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.

SUBMITTER: Salihovic A 

PROVIDER: S-EPMC11368039 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature

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Gram-scale enzymatic synthesis of 2'-deoxyribonucleoside analogues using nucleoside transglycosylase-2.

Salihovic Admir A   Ascham Alex A   Taladriz-Sender Andrea A   Bryson Samantha S   Withers Jamie M JM   McKean Iain J W IJW   Hoskisson Paul A PA   Grogan Gideon G   Burley Glenn A GA  

Chemical science 20240827


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'-deoxyribosyltransfe  ...[more]

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