Biased Borate Esterification during Nucleoside Phosphorylase-Catalyzed Reactions: Apparent Equilibrium Shifts and Kinetic Implications** |
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| Authors: | Dr. Felix Kaspar Felix Brandt Sarah Westarp Lea Eilert Dr. Sebastian Kemper Dr. Anke Kurreck Prof. Dr. Peter Neubauer Prof. Dr. Christoph R. Jacob Prof. Dr. Anett Schallmey |
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| Affiliation: | 1. Institute for Biochemistry, Biotechnology and Bioinformatics, Technische Universität Braunschweig, Spielmannstraße 7, 38106 Braunschweig, Germany;2. Institute of Physical and Theoretical Chemistry, Technische Universität Braunschweig, Gaußstraße 17, 38106 Braunschweig, Germany;3. Chair of Bioprocess Engineering, Institute of Biotechnology, Faculty III Process Sciences, Technische Universität Berlin, Ackerstraße 76, 13355 Berlin, Germany;4. Institute for Chemistry, Technische Universität Berlin, Straße des 17. Juni 135, 10623 Berlin, Germany |
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| Abstract: | Biocatalytic nucleoside (trans-)glycosylations catalyzed by nucleoside phosphorylases have evolved into a practical and convenient approach to the preparation of modified nucleosides, which are important pharmaceuticals for the treatment of various cancers and viral infections. However, the obtained yields in these reactions are generally determined exclusively by the innate thermodynamic properties of the nucleosides involved, hampering the biocatalytic access to many sought-after target nucleosides. We herein report an additional means for reaction engineering of these systems. We show how apparent equilibrium shifts in phosphorolysis and glycosylation reactions can be effected through entropically driven, biased esterification of nucleosides and ribosyl phosphates with inorganic borate. Our multifaceted analysis further describes the kinetic implications of this in situ reactant esterification for a model phosphorylase. |
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| Keywords: | Biocatalysis Borate Ester Equilibrium Nucleoside Analogues Phosphorolyase |
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