Gram-scale enzymatic synthesis of 2′-deoxyribonucleoside analogues using nucleoside transglycosylase-2
Salihovic, Admir and Ascham, Alex and Taladriz-Sender, Andrea and Bryson, Samantha and Withers, Jamie M. and Mckean, Iain J. W. and Hoskisson, Paul A. and Grogan, Gideon and Burley, Glenn A. (2024) Gram-scale enzymatic synthesis of 2′-deoxyribonucleoside analogues using nucleoside transglycosylase-2. Chemical Science. ISSN 2041-6539 (https://doi.org/10.1039/D4SC04938A)
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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.
ORCID iDs
Salihovic, Admir, Ascham, Alex, Taladriz-Sender, Andrea ORCID: https://orcid.org/0000-0002-8274-4761, Bryson, Samantha, Withers, Jamie M. ORCID: https://orcid.org/0000-0002-9746-9467, Mckean, Iain J. W. ORCID: https://orcid.org/0000-0002-4970-1508, Hoskisson, Paul A. ORCID: https://orcid.org/0000-0003-4332-1640, Grogan, Gideon and Burley, Glenn A.;-
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Item type: Article ID code: 90459 Dates: DateEvent27 August 2024Published27 August 2024Published Online26 August 2024AcceptedSubjects: Science > Chemistry
Medicine > Pharmacy and materia medica > Pharmaceutical chemistryDepartment: Faculty of Science > Pure and Applied Chemistry
Faculty of Science > Strathclyde Institute of Pharmacy and Biomedical Sciences
Technology and Innovation Centre > BionanotechnologyDepositing user: Pure Administrator Date deposited: 03 Sep 2024 14:40 Last modified: 01 Oct 2024 07:06 Related URLs: URI: https://strathprints.strath.ac.uk/id/eprint/90459