Thermodynamic reaction control of nucleoside phosphorolysis

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dc.contributor.authorKaspar, Felix
dc.contributor.authorGiessmann, Robert T.
dc.contributor.authorNeubauer, Peter
dc.contributor.authorWagner, Anke
dc.contributor.authorGimpel, Matthias
dc.date.accessioned2020-02-26T13:01:13Z
dc.date.available2020-02-26T13:01:13Z
dc.date.issued2020-01-07
dc.description.abstractNucleoside 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.en
dc.description.sponsorshipDFG, 390540038, EXC 2008: UniSysCaten
dc.description.sponsorshipTU Berlin, Open-Access-Mittel - 2019en
dc.identifier.eissn1615-4169
dc.identifier.issn1615-4150
dc.identifier.urihttps://depositonce.tu-berlin.de/handle/11303/10842
dc.identifier.urihttp://dx.doi.org/10.14279/depositonce-9737
dc.language.isoen
dc.relation.ispartof10.14279/depositonce-10629en
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subject.ddc540 Chemie und zugeordnete Wissenschaftenen
dc.subject.ddc660 Chemische Verfahrenstechniken
dc.subject.othernucleosidesen
dc.subject.othernucleoside phosphorylaseen
dc.subject.othernucleoside phosphorolysisen
dc.subject.otherequilibrium constanten
dc.subject.othertemperatureen
dc.titleThermodynamic reaction control of nucleoside phosphorolysisen
dc.typeArticleen
dc.type.versionpublishedVersionen
dcterms.bibliographicCitation.doi10.1002/adsc.201901230
dcterms.bibliographicCitation.issue4
dcterms.bibliographicCitation.journaltitleAdvanced Synthesis & Catalysisen
dcterms.bibliographicCitation.originalpublishernameWileyen
dcterms.bibliographicCitation.originalpublisherplaceWeinheimen
dcterms.bibliographicCitation.pageend876
dcterms.bibliographicCitation.pagestart867
dcterms.bibliographicCitation.volume362
tub.accessrights.dnbfree
tub.affiliationFak. 3 Prozesswissenschaften::Inst. Biotechnologie::FG Bioverfahrenstechnikde
tub.affiliation.facultyFak. 3 Prozesswissenschaftende
tub.affiliation.groupFG Bioverfahrenstechnikde
tub.affiliation.instituteInst. Biotechnologiede
tub.publisher.universityorinstitutionTechnische Universität Berlinde

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