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

References

  1. Del Arco J., Acosta J., Fernández-Lucas J. // Biotechnol. Adv. 2021. V. 51. P. 107701. https://doi.org/10.1016/j.biotechadv.2021.107701
  2. Uchikubo Y., Hasegawa T., Mitani S., Kim H.-S., Wataya Y. // Nucleic Acids Res. Suppl. 2002. V. 2. P. 245–246. https://doi.org/10.1093/nass/2.1.245
  3. Goz B. // Pharmacol. Rev. 1977. V. 29. P. 249–272.
  4. Gulick R.M., Mellors J.W., Havlir D., Eron J.J., Gonzalez C., McMahon D., Richman D.D., Valentine F.T., Jonas L., Meibohm A., Emini E.A., Chodakewitz J.A. // N. Engl. J. Med. 1997. V. 337. P. 734–739. https://doi.org/10.1056/NEJM199709113371102
  5. Sacks S.L., Tyrrell L.D., Lawee D., Schlech W., 3rd, Gill M.J., Aoki F.Y., Martel A.Y., Singer J. // J. Infect. Dis. 1991. V. 164. P. 665–672. https://doi.org/10.1093/infdis/164.4.665
  6. De Clercq E. // Antivir. Chem. Chemother. 2013. V. 23. P. 93–101. https://doi.org/10.3851/IMP2533
  7. Fukushima M., Suzuki N., Emura T., Yano S., Kazuno H., Tada Y., Yamada Y., Asao T. // Biochem. Pharmacol. 2000. V. 59. P. 1227–1236. https://doi.org/10.1016/s0006-2952(00)00253-7
  8. Lenz H.J., Stintzing S., Loupakis F. // Cancer Treat. Rev. 2015. V. 41. P. 777–783. https://doi.org/10.1016/j.ctrv.2015.06.001
  9. Mikhailopulo I.A., Miroshnikov A.I. // Mendeleev Commun. 2011. V. 21. P. 57–68. https://doi.org/10.1016/j.mencom.2011.03.001
  10. Alexeev C.S., Kulikova I.V., Gavryushov S., Tararov V.I., Mikhailov S.N. // Adv. Synth. Catal. 2018. V. 360. P. 3090–3096. https://doi.org/10.1002/adsc.201800411
  11. Alexeev C.S., Drenichev M.S., Dorinova E.O., Esipov R.S., Kulikova I.V., Mikhailov S.N. // Biochim. Biophys. Acta Proteins Proteom. 2020. V. 1868. P. 140292. https://doi.org/10.1016/j.bbapap.2019.140292
  12. Kaspar F., Giessmann R.T., Neubauer P., Wagner A., Gimpel M. // Adv. Synth. Catal. 2020. V. 362. P. 867– 876. https://doi.org/10.1002/adsc.201901230
  13. Holguin J., Cardinaud R. // Eur. J. Biochem. 1975. V. 54. P. 505–514. https://doi.org/10.1111/j.1432-1033.1975.tb04163.x
  14. Kaminski P.A. // J. Biol. Chem. 2002. V. 277. P. 14400–14407. https://doi.org/10.1074/jbc.M111995200
  15. Fresco-Taboada A., De la Mata I., Arroyo M., Fernández-Lucas J. // Appl. Microbiol. Biotechnol. 2013. V. 97. P. 3773–3785. https://doi.org/10.1007/s00253-013-4816-y
  16. Becker J., Brendel M. // Biol. Chem. Hoppe Seyler. 1996. V. 377. P. 357–362. https://doi.org/10.1515/bchm3.1996.377.6.357
  17. Crespo N., Sánchez-Murcia P.A., Gago F., CejudoSanches J., Galmes M.A., Fernández-Lucas J., Mancheño J.M. // Appl. Microbiol. Biotechnol. 2017. V. 101. P. 7187–7200. https://doi.org/10.1007/s00253-017-8450-y
  18. Pérez E., Sánchez-Murcia P.A., Jordaan J., Blanco M.D., Mancheño J.M., Gago F., Fernández-Lucas J. // Chem. Cat. Chem. 2018. V. 10. P. 4406–4416. https://doi.org/10.1002/cctc.201800775
  19. Cardinaud R., Holguin J. // Biochim. Biophys. Acta Enzymol. 1979. V. 568. P. 339–347. https://doi.org/10.1016/0005-2744(79)90301-2
  20. Fernández-Lucas J., Acebal C., Sinisterra J.V., Arroyo M., de la Mata I. // Appl. Environ. Microbiol. 2010. V. 76. P. 1462–1470. https://doi.org/10.1128/AEM.01685-09
  21. Schnetz-Boutaud N.C., Chapeau M.C., Marnett L.J. // Curr. Protoc. Nucleic Acid Chem. 2001. Ch. 1. Unit 1.2. https://doi.org/10.1002/0471142700.nc0102s00
  22. Drenichev M.S., Alexeev C.S., Kurochkin N.N., Mikhailov S.N. // Adv. Synth. Catal. 2018. V. 360. P. 305–312. https://doi.org/10.1002/adsc.201701005
  23. Константинова И.Д., Антонов К.В., Берзин В.Б., Дорофеева Е.В., Фатеев И.В., Музыка И.С., Мирошников А.И. // Патент RU2368662С1, опубл. 27.09.2009.
  24. Zuffi G., Monciardini S. // Patent US8012717B2, published 06.09.2011.
  25. Salihovic A., Ascham A., Taladriz-Sender A., Bryson S., Withers J.M., McKean I.J.W., Hoskisson P.A., Grogan G., Burley G.A. // Chem. Sci. 2024. V. 15. P. 15399– 15407. https://doi.org/10.1039/d4sc04938a
  26. Konkina M.A., Drenichev M.S., Nasyrova D.I., Porozov Y.B., Alexeev C.S. // Sustain. Chem. Pharm. 2023. V. 32. P. 101011. https://doi.org/10.1016/j.scp.2023.101011
  27. Rabuffetti M., Bavaro T., Semproli R., Cattaneo G., Massone M., Morelli C.F., Speranza G., Ubiali D. // Catal. 2019. V. 9. P. 355. https://doi.org/10.3390/catal9040355
  28. Van Aerschot A., Everaert D., Balzarini J., Augustyns K., Jie L., Janssen G., Peeters O., Blaton N., De Ranter C., De Clercq E. // J. Med. Chem. 1990. V. 33. P. 1833–1839. https://doi.org/10.1021/jm00168a046

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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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