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Diversification of 4ʹ-Methylated Nucleosides by Nucleoside Phosphorylases
preprintsubmitted on 13.04.2021, 08:18 and posted on 15.04.2021, 04:58 by Felix Kaspar, Margarita Seeger, Sarah Westarp, Christoph Köllmann, Anna P. Lehmann, Patrick Pausch, Sebastian Kemper, Peter Neubauer, Gert Bange, Anett Schallmey, Daniel Werz, Anke Kurreck
The growing demand for 4'-modified nucleoside analogs in medicinal and biological chemistry is contrasted by the challenging synthetic access to these molecules and the lack of efficient diversification strategies. Herein, we report the development of a biocatalytic diversification approach based on nucleoside phosphorylases, which allows the straightforward installation of a variety of pyrimidine and purine nucleobases on a 4'-alkylated sugar scaffold. Following the identification of a suitable biocatalyst as well as its characterization with kinetic experiments and docking studies, we systematically explored the equilibrium thermodynamics of this reaction system to enable rational yield prediction in transglycosylation reactions via principles of thermodynamic control.