Enzymatic Synthesis of Nucleoside Analogues by Nucleoside Phosphorylases

Kamel, Sarah; Yehia, Heba; Neubauer, Peter; Wagner, Anke

doi:10.1002/9783527812103.ch1

Cited by 36 publications

(45 citation statements)

References 126 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…[2] Biocatalytic methods are a valuable alternative as pyrimidine and purine nucleosides can be synthesized with high selectivity in sustainable enzyme-catalyzed processes. [3] Here, the use of nucleoside phosphorylases (NPases) has been firmly established and these enzymes are widely applied for the synthesis of nucleosides and their analogues. [3] NPases catalyze the phosphorolysis of nucleosides to pentose-1-phosphates, as well as the corresponding reverse reaction (Scheme 1).…”

Section: Introductionmentioning

confidence: 99%

“…[3] Here, the use of nucleoside phosphorylases (NPases) has been firmly established and these enzymes are widely applied for the synthesis of nucleosides and their analogues. [3] NPases catalyze the phosphorolysis of nucleosides to pentose-1-phosphates, as well as the corresponding reverse reaction (Scheme 1). They are generally classified as either pyrimidine nucleoside phosphorylases (Py-NPases) or purine nucleoside phosphorylases (Pu-NPases), depending on their substrate spectra.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Thermodynamic Reaction Control of Nucleoside Phosphorolysis

et al. 2020

Self Cite

View full text Add to dashboard Cite

Nucleoside analogs represent a class of important drugs for cancer and antiviral treatments. Nucleoside phosphorylases (NPases) catalyze the phosphorolysis of nucleosides and are widely employed for the synthesis of pentose‐1‐phosphates and nucleoside analogs, which are difficult to access via conventional synthetic methods. However, for the vast majority of nucleosides, it has been observed that either no or incomplete conversion of the starting materials is achieved in NPase‐catalyzed reactions. For some substrates, it has been shown that these reactions are reversible equilibrium reactions that adhere to the law of mass action. In this contribution, we broadly demonstrate that nucleoside phosphorolysis is a thermodynamically controlled endothermic reaction that proceeds to a reaction equilibrium dictated by the substrate‐specific equilibrium constant of phosphorolysis, irrespective of the type or amount of NPase used, as shown by several examples. Furthermore, we explored the temperature‐dependency of nucleoside phosphorolysis equilibrium states and provide the apparent transformed reaction enthalpy and apparent transformed reaction entropy for 24 nucleosides, confirming that these conversions are thermodynamically controlled endothermic reactions. This data allows calculation of the Gibbs free energy and, consequently, the equilibrium constant of phosphorolysis at any given reaction temperature. Overall, our investigations revealed that pyrimidine nucleosides are generally more susceptible to phosphorolysis than purine nucleosides. The data disclosed in this work allow the accurate prediction of phosphorolysis or transglycosylation yields for a range of pyrimidine and purine nucleosides and thus serve to empower further research in the field of nucleoside biocatalysis.

show abstract

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Thermodynamic Reaction Control of Nucleoside Phosphorolysis

et al. 2020

Self Cite

View full text Add to dashboard Cite

show abstract

“…Numerous reviews on nucleoside phosphorylases are available. The structural organization of these enzymes [1,2], the substrate specificity and methods for the synthesis of valuable nucleosides [3][4][5][6], and metabolism in biological systems [7][8][9][10] have been considered.…”

Section: Nucleoside Phosphorylases As Key Enzymes In Nucleoside Metabmentioning

confidence: 99%

“…This enzyme acts as a dimer. Uridine, deoxyuridine, and thymidine are substrates for UPs [1,6,27]. Meanwhile, cytidine can also serves as a substrate for S. cerevisiae UP [28].…”

Section: Nucleoside Phosphorylases As Key Enzymes In Nucleoside Metabmentioning

confidence: 99%

Strained Conformations of Nucleosides in Active Sites of Nucleoside Phosphorylases

2020

View full text Add to dashboard Cite

Nucleoside phosphorylases catalyze the reversible phosphorolysis of nucleosides to heterocyclic bases, giving α-d-ribose-1-phosphate or α-d-2-deoxyribose-1-phosphate. These enzymes are involved in salvage pathways of nucleoside biosynthesis. The level of these enzymes is often elevated in tumors, which can be used as a marker for cancer diagnosis. This review presents the analysis of conformations of nucleosides and their analogues in complexes with nucleoside phosphorylases of the first (NP-1) family, which includes hexameric and trimeric purine nucleoside phosphorylases (EC 2.4.2.1), hexameric and trimeric 5′-deoxy-5′-methylthioadenosine phosphorylases (EC 2.4.2.28), and uridine phosphorylases (EC 2.4.2.3). Nucleosides adopt similar conformations in complexes, with these conformations being significantly different from those of free nucleosides. In complexes, pentofuranose rings of all nucleosides are at the W region of the pseudorotation cycle that corresponds to the energy barrier to the N↔S interconversion. In most of the complexes, the orientation of the bases with respect to the ribose is in the high-syn region in the immediate vicinity of the barrier to syn ↔ anti transitions. Such conformations of nucleosides in complexes are unfavorable when compared to free nucleosides and they are stabilized by interactions with the enzyme. The sulfate (or phosphate) ion in the active site of the complexes influences the conformation of the furanose ring. The binding of nucleosides in strained conformations is a characteristic feature of the enzyme–substrate complex formation for this enzyme group.

show abstract

“…[2][3][4][5] Biocatalytic methods offer the efficient and protecting group-free synthesis of pyrimidine and purine nucleosides. The use of nucleoside phosphorylases (NPases) for the preparation of nucleosides and their analogues in transglycosylation reactions is firmly established [6] and numerous examples of enzymatic or chemoenzymatic syntheses can be found in the literature. [7][8][9][10][11][12][13][14] NPases catalyze the reversible phosphorolysis of nucleosides to pentose-1-phosphates (Scheme 1, I).…”

mentioning

confidence: 99%

General Principles for Yield Optimization of Nucleoside Phosphorylase-Catalyzed Transglycosylations

Kaspar¹,

Giessmann²,

Hellendahl³

et al. 2019

Preprint

Self Cite

View full text Add to dashboard Cite

This is our publication "General Principles for Yield Optimization of Nucleoside Phosphorylase-Catalyzed Transglycosylations" that described the prediction and optimization of yields in nucleoside transglycosylations mediated by nucleoside phosphorylases. As a continuation to previous reports, we highlight the varying effect of excess phosphate on product yield both theoretically and experimentally, as this is a crucially important feature of the reaction system previous undecribed. Furthermore, we provide a simplified equation for the estimation of product yield that allows for straightforward analytical solutions instead of the numerical solutions previously required. Herein, we provide the full text draft of our work along with the supplementary information. Externally hosted supplementary files can be accessed via the links cited in the main document.

show abstract

Enzymatic Synthesis of Nucleoside Analogues by Nucleoside Phosphorylases

Cited by 36 publications

References 126 publications

Thermodynamic Reaction Control of Nucleoside Phosphorolysis

Thermodynamic Reaction Control of Nucleoside Phosphorolysis

Strained Conformations of Nucleosides in Active Sites of Nucleoside Phosphorylases

General Principles for Yield Optimization of Nucleoside Phosphorylase-Catalyzed Transglycosylations

Contact Info

Product

Resources

About