Diversification of 4ʹ-Methylated Nucleosides by Nucleoside Phosphorylases

15 April 2021, Version 1
This content is a preprint and has not undergone peer review at the time of posting.


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.


equilibrium allele distributions
nucleoside analogue

Supplementary materials

SI Me-nucleosides ChemRxiv

Supplementary weblinks


Comments are not moderated before they are posted, but they can be removed by the site moderators if they are found to be in contravention of our Commenting Policy [opens in a new tab] - please read this policy before you post. Comments should be used for scholarly discussion of the content in question. You can find more information about how to use the commenting feature here [opens in a new tab] .
This site is protected by reCAPTCHA and the Google Privacy Policy [opens in a new tab] and Terms of Service [opens in a new tab] apply.