Enzymatic Synthesis of Biologically Active 5-Substituted Analogues of 2ʹ-Deoxyuridine by Lactobacillus leichmannii Nucleoside Deoxyribosyltransferase Type II

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Abstract

Enzymatic transglycosylation reactions catalysed by Lactobacillus leichmannii nucleoside deoxyribosyltransferase type II in the presence of 7-methyl-2′-deoxyguanosine and modified pyrimidine heterocyclic bases were studied. The choice of 7-methyl-2′-deoxyguanosine as a nucleoside donor of a carbohydrate residue allowed the enzymatic synthesis of 5-substituted 2′-deoxyuridine derivatives in high yields. Biologically active 2ʹ-deoxyuridine derivatives were obtained, three ones currently used in clinical practice in antiviral and antitumour therapy. The selected enzyme-catalyst, initial ratios of molar concentrations of substrates and the selected nucleoside-donor – source of carbohydrate residue will make it possible to develop environmentally friendly biochemical methods for the preparation of practically important modified nucleosides.

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About the authors

C. S. Alexeev

Engelhardt Institute of Molecular Biology, Russian Academy of Sciences

Author for correspondence.
Email: micelle@mail.ru
Russian Federation, ul. Vavilova 32, Moscow, 119991

A. M. Sergievskaia

MIREA Russian Technological University

Email: micelle@mail.ru

Lomonosov Institute of Fine Chemical Technologies

Russian Federation, prosp. Vernadskogo 86, Moscow, 119571

D. A. Platov

Engelhardt Institute of Molecular Biology, Russian Academy of Sciences; MIREA Russian Technological University

Email: micelle@mail.ru

Lomonosov Institute of Fine Chemical Technologies

Russian Federation, ul. Vavilova 32, Moscow, 119991; prosp. Vernadskogo 86, Moscow, 119571

M. S. Drenichev

Engelhardt Institute of Molecular Biology, Russian Academy of Sciences

Email: micelle@mail.ru
Russian Federation, ul. Vavilova 32, Moscow, 119991

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2. Figure 1.5-Substituted derivatives of 2'-deoxyuridine used in antiviral and antitumor therapy.

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3. 2. Enzymatic synthesis of 5-I-dUrd. Conditions: 25 mM HEPES, pH 7.4, 20°C, NDT II L. leichmanii, concentrations of acceptor and donor were 0.2 and 0.6 mM (ratio 1 : 3).

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4. Scheme 1. Enzymatic transglycosylation reaction catalyzed by nucleoside phosphorylases (NP). B1 and B2 are purine and/or pyrimidine heterocyclic bases.

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5. Scheme 2. Enzymatic transglycosylation reaction catalyzed by nucleoside deoxyribosyltransferase (NDT). B1 and B2 are purine and/or pyrimidine heterocyclic bases.

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