Diversification of 4′-Methylated Nucleosides by Nucleoside Phosphorylases

ACS Catalysis ◽  
2021 ◽  
Vol 11 (17) ◽  
pp. 10830-10835
Author(s):  
Felix Kaspar ◽  
Margarita Seeger ◽  
Sarah Westarp ◽  
Christoph Köllmann ◽  
Anna P. Lehmann ◽  
...  
Keyword(s):  
Nucleoside Phosphorylases

scholarly journals Enzymatic synthesis and phosphorolysis of 4(2)-thioxo- and 6(5)-azapyrimidine nucleosides by E. coli nucleoside phosphorylases

2016 ◽  
Vol 12 ◽  
pp. 2588-2601 ◽  
Author(s):  
Vladimir A Stepchenko ◽  
Anatoly I Miroshnikov ◽  
Frank Seela ◽  
Igor A Mikhailopulo
Keyword(s):  
Purine Nucleoside Phosphorylase ◽  
Reaction Conditions ◽  
E Coli ◽  
No Formation ◽  
Structural Peculiarities ◽  
Substrate Properties ◽  
Nucleoside Phosphorylases ◽  
Derivatives Of

The trans-2-deoxyribosylation of 4-thiouracil (4SUra) and 2-thiouracil (2SUra), as well as 6-azauracil, 6-azathymine and 6-aza-2-thiothymine was studied using dG and E. coli purine nucleoside phosphorylase (PNP) for the in situ generation of 2-deoxy-α-D-ribofuranose-1-phosphate (dRib-1P) followed by its coupling with the bases catalyzed by either E. coli thymidine (TP) or uridine (UP) phosphorylases. 4SUra revealed satisfactory substrate activity for UP and, unexpectedly, complete inertness for TP; no formation of 2’-deoxy-2-thiouridine (2SUd) was observed under analogous reaction conditions in the presence of UP and TP. On the contrary, 2SU, 2SUd, 4STd and 2STd are good substrates for both UP and TP; moreover, 2SU, 4STd and 2’-deoxy-5-azacytidine (Decitabine) are substrates for PNP and the phosphorolysis of the latter is reversible. Condensation of 2SUra and 5-azacytosine with dRib-1P (Ba salt) catalyzed by the accordant UP and PNP in Tris∙HCl buffer gave 2SUd and 2’-deoxy-5-azacytidine in 27% and 15% yields, respectively. 6-Azauracil and 6-azathymine showed good substrate properties for both TP and UP, whereas only TP recognizes 2-thio-6-azathymine as a substrate. 5-Phenyl and 5-tert-butyl derivatives of 6-azauracil and its 2-thioxo derivative were tested as substrates for UP and TP, and only 5-phenyl- and 5-tert-butyl-6-azauracils displayed very low substrate activity. The role of structural peculiarities and electronic properties in the substrate recognition by E. coli nucleoside phosphorylases is discussed.

Chemo-enzymatic synthesis of α-d-pentofuranose-1-phosphates using thermostable pyrimidine nucleoside phosphorylases

2018 ◽  
Vol 458 ◽  
pp. 52-59 ◽  
Author(s):  
Sarah Kamel ◽  
Max Weiß ◽  
Hendrik F.T. Klare ◽  
Igor A. Mikhailopulo ◽  
Peter Neubauer ◽  
...  
Keyword(s):  
Enzymatic Synthesis ◽  
Pyrimidine Nucleoside ◽  
Nucleoside Phosphorylases

scholarly journals Xanthine, xanthosine and its nucleotides: solution structures of neutral and ionic forms, and relevance to substrate properties in various enzyme systems and metabolic pathways.

2004 ◽  
Vol 51 (2) ◽  
pp. 493-531 ◽  
Author(s):  
Ewa Kulikowska ◽  
Borys Kierdaszuk ◽  
David Shugar
Keyword(s):  
Metabolic Pathways ◽  
Equilibrium Mixture ◽  
Solution Structures ◽  
Enzyme Systems ◽  
Alkyl Derivatives ◽  
Substrate Properties ◽  
Nucleoside Hydrolases ◽  
Nucleoside Phosphorylases ◽  
Xanthine Nucleotide ◽  
Striking Contrast

The 6-oxopurine xanthine (Xan, neutral form 2,6-diketopurine) differs from the corresponding 6-oxopurines guanine (Gua) and hypoxanthine (Hyp) in that, at physiological pH, it consists of a approximately 1:1 equilibrium mixture of the neutral and monoanionic forms, the latter due to ionization of N(3)-H, in striking contrast to dissociation of the N(1)-H in both Gua and Hyp at higher pH. In xanthosine (Xao) and its nucleotides the xanthine ring is predominantly, or exclusively, a similar monoanion at physiological pH. The foregoing has, somewhat surprisingly, been widely overlooked in studies on the properties of these compounds in various enzyme systems and metabolic pathways, including, amongst others, xanthine oxidase, purine phosphoribosyltransferases, IMP dehydrogenases, purine nucleoside phosphorylases, nucleoside hydrolases, the enzymes involved in the biosynthesis of caffeine, the development of xanthine nucleotide-directed G proteins, the pharmacological properties of alkylxanthines. We here review the acid/base properties of xanthine, its nucleosides and nucleotides, their N-alkyl derivatives and other analogues, and their relevance to studies on the foregoing. Included also is a survey of the pH-dependent helical forms of polyxanthylic acid, poly(X), its ability to form helical complexes with a broad range of other synthetic homopolynucleotides, the base pairing properties of xanthine in synthetic oligonucleotides, and in damaged DNA, as well as enzymes involved in circumventing the existence of xanthine in natural DNA.

scholarly journals The Peculiar Case of the Hyperthermostable Pyrimidine Nucleoside Phosphorylase from Thermus Thermophilus

2020 ◽  
Author(s):  
Felix Kaspar ◽  
Peter Neubauer ◽  
Anke Kurreck
Keyword(s):  
Thermus Thermophilus ◽  
Pyrimidine Nucleoside ◽  
Reaction Conditions ◽  
Nucleoside Phosphorylase ◽  
Pyrimidine Nucleosides ◽  
Low Concentrations ◽  
Pyrimidine Nucleoside Phosphorylase ◽  
Total Turnover ◽  
Nucleoside Phosphorylases ◽  
Peculiar Case

The poor solubility of many nucleoside and nucleobases in aqueous solution demands harsh reaction conditions (base, heat, cosolvent) in nucleoside phosphorylase-catalyzed processes to facilitate substrate loading beyond the low millimolar range. This, in turn, requires enzymes which withstand these conditions. Herein we report that the pyrimidine nucleoside phosphorylase from <i>Thermus thermophilus</i> is active over an exceptionally broad pH (4-10), temperature (up to 100 °C) and cosolvent space (up to 80% (v/v) non-aqueous medium) and displays tremendous stability under harsh reaction conditions with predicted total turnover numbers of more than 10<sup>6</sup> for various pyrimidine nucleosides. However, its use as a biocatalyst for preparative applications is critically limited due to its inhibition by nucleoside substrates at low concentrations, which is unprecedented among non-specific pyrimidine nucleoside phosphorylases.<br>

Interactions of Trimeric Purine Nucleoside Phosphorylases with Ground State Analogues — Calorimetric and Fluorimetric Studies

ChemInform ◽  
2004 ◽  
Vol 35 (9) ◽  
Author(s):  
Beata Wielgus-Kutrowska ◽  
Joachim Frank ◽  
Antonin Holy ◽  
Gertraud Koellner ◽  
Agnieszka Bzowska
Keyword(s):  
Ground State ◽  
Purine Nucleoside ◽  
Nucleoside Phosphorylases

Developing a Collection of Immobilized Nucleoside Phosphorylases for the Preparation of Nucleoside Analogues: Enzymatic Synthesis of Arabinosyladenine and 2′,3′-Dideoxyinosine

ChemPlusChem ◽  
2012 ◽  
Vol 78 (2) ◽  
pp. 157-165 ◽  
Author(s):  
Immacolata Serra ◽  
Daniela Ubiali ◽  
Jure Piškur ◽  
Stig Christoffersen ◽  
Elizabeth S. Lewkowicz ◽  
...  
Keyword(s):  
Enzymatic Synthesis ◽  
Nucleoside Analogues ◽  
Nucleoside Phosphorylases

Localization of purine and pyrimidine nucleoside phosphorylases in heart, kidney, and liver

1980 ◽  
Vol 239 (6) ◽  
pp. H721-H730 ◽  
Author(s):  
R. Rubio ◽  
R. M. Berne
Keyword(s):  
Guinea Pig ◽  
Kupffer Cells ◽  
Cellular Localization ◽  
Purine Nucleoside Phosphorylase ◽  
Degradation Products ◽  
Purine Nucleoside ◽  
Capillary Endothelium ◽  
Cell Fractionation ◽  
Nucleoside Phosphorylase ◽  
Nucleoside Phosphorylases

In isolated livers and kidneys perfused with Krebs-Henseleit solution, the relationship of the concentration of adenosine (Ado) to that of its degradation products inosine (Ino) and hypoxanthine (Hyp) in biliary, urinary, and venous effluents were determined. They revealed ratios of Hyp:Ado:Ino, 1.9:1:0.9, 0.7:1:0.6, and 1.3:1:0.5 for guinea pig biliary, guinea pig urinary, and rat urinary effluents, respectively, and their respective venous effluent were 58:1:29, 8.6:1:5.4, and 7.4:1:3.2. The greater proportion of Ino and Hyp in the venous effluents suggests active production in Ino and Hyp at the vessel wall. Purine nucleoside phosphorylase localization was determined histochemically and found most active in the cytoplasm of capillary endothelium and Kupffer cells. Thus, there is agreement between purine analysis and histochemical findings. The reliability of the histochemical technique was also tested by comparing activities of purine nucleoside phosphorylase (a cytoplasmic enzyme) and pyrmidine nucleoside phosphorylase (a nuclear enzyme) that catalyze similar reactions (nucleoside + inorganic phosphate in equilibrium base + ribose-1-phosphate) but with different base specificites and cellular localization, as indicated by cell fractionation studies. The histochemical results show that in contrast to the purine nucleoside phosphorylase, the pyrmidine specific enzyme was most active in the nuclei of endothelial and Kupffer cells. Thus, the technique discriminates between the two enzymes.

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