Preparation of 6-azido-2-chloropurine-2′-deoxyriboside by enzymatic transglycosylation reaction catalyzed by Lactobacillus leichmannii type 2 nucleoside deoxyribosyltransferase

Cover Page

Cite item

Full Text

Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription or Fee Access

Abstract

6-azido-2-chloropurine-2′-deoxyriboside, a valuable precursor for the preparation of modified 2-chloropurine nucleosides substituted at the 6-position of the heterocyclic base, was obtained by enzymatic transglycosylation. 6-azido-2-chloropurine-2′-deoxyriboside can also be used as a photocross-linking agent to study the nucleic acids – proteins interactions. A type 2 nucleoside deoxyribosyltransferase from Lactobacillus leichmannii was used as a biocatalyst. The optimal conditions for the formation of 6-azido-2-chloropurine-2′-deoxyriboside using 7-methyl-2′-deoxyguanosine as a carbohydrate residue donor were determined.

About the authors

C. S. Alexeev

Engelhardt Institute of Molecular Biology, Russian Academy of Sciences

Email: micelle@mail.ru
Moscow, Russian Federation

M. A. Konkina

Engelhardt Institute of Molecular Biology, Russian Academy of Sciences; Lomonosov Institute of Fine Chemical Technologies, MIREA Russia Technological University

Email: cyril.alex@eimb.ru
Moscow, Russian Federation; Moscow, Russian Federation

N. N. Kurochkin

Engelhardt Institute of Molecular Biology, Russian Academy of Sciences

Email: micelle@mail.ru
Moscow, Russian Federation

M. S. Drenichev

Engelhardt Institute of Molecular Biology, Russian Academy of Sciences

Author for correspondence.
Email: micelle@mail.ru
Moscow, Russian Federation

References

  1. Iglesias L.E., Lewkowicz E. S., Medici R., et al. Biocatalytic approaches applied to the synthesis of nucleoside prodrugs // Biotechnol. Adv. 2015, Vol. 33, N5. P. 412–434. doi: 10.1016/j.biotechadv.2015.03.009
  2. Holguin J., Cardinaud R. Trans-N-Deoxyribosylase: Purification by Affinity Chromatography and Characterization // Eur. J. Biochem. 1975. Vol. 54, N2. P. 505–514. PMID: 1175596. https://doi.org/10.1111/j.1432–1033.1975.tb04163.x;
  3. Kaminski P. A. Functional Cloning, Heterologous Expression, and Purification of Two Different N-Deoxyribosyltransferases from Lactobacillus helveticus // J. Biol. Chem. 2002. Vol. 277, N17. P. 14400–14407. PMID: 11836245. https://doi.org/10.1074/jbc.M111995200
  4. Del Arco J., Perona A., González L., et al. Reaction mechanism of nucleoside 2′-deoxyribosyltransferases: free-energy landscape supports an oxocarbenium ion as the reaction intermediate. // Org. Biomol. Chem. 2019. Vol. 17, N34. P. 7891–7899. https://doi.org/10.1039/c9ob01315f.
  5. Becker J., Brendel M. Rapid Purification and Characterization of Two Distinct N-Deoxyribosyltransferases of Lactobacillus leichmannii // Biol. Chem. Hoppe Seyler. 1996. Vol. 377, N6. P. 357–362. PMID: 8839981. https://doi.org/10.1515/bchm3.1996.377.6.357
  6. Crespo N, Sánchez-Murcia P. A., Gago F., et. al. 2′-Deoxyribosyltransferase from Leishmania mexicana, an efficient biocatalyst for one-pot, one-step synthesis of nucleosides from poorly soluble purine bases // Appl. Microbiol. Biotechnol. 2017. Vol. 101, N19. P. 7187–7200. PMID: 28785897. https://doi.org/10.1007/s00253-017-8450-y
  7. Pérez E., Sánchez-Murcia P. A., Jordaan J., et. al. Enzymatic Synthesis of Therapeutic Nucleosides using a Highly Versatile Purine Nucleoside 2'-DeoxyribosylTransferase from Trypanosoma brucei // Chem. Cat. Chem. 2018. Vol. 10, N19. P. 4406–4416. https://doi.org/10.1002/cctc.201800775
  8. Cardinaud R, Holguin J. Nucleoside deoxyribosyltransferase-II from Lactobacillus helveticus. Substrate specificity studies. Pyrimidine bases as acceptors // Biochim. Biophys. Acta – Enzymology. 1979. Vol. 568, N2. P. 339–347. PMID: 486487. https://doi.org/10.1016/0005-2744(79)90301-2
  9. Fernández-Lucas J., Acebal C., Sinisterra J. V., et al. Lactobacillus reuteri 2′-Deoxyribosyltransferase, a Novel Biocatalyst for Tailoring of Nucleosides // Appl. Environ. Microbiol. 2010. Vol. 76, N5. P. 1462–1470. PMID: 20048065; PMCID: PMC2832402. https://doi.org/10.1128/AEM.01685-09
  10. Del Arco J., Acosta J., Fernández-Lucas J. New trends in the biocatalytic production of nucleosidic active pharmaceutical ingredients using 2′-deoxyribosyltransferases // Biotechnol. Adv. 2021. Vol. 51. P. 107701. PMID: 33515673 https://doi.org 10.1016/ j.biotechadv.2021.107701
  11. Kovaļovs A., Novosjolova I, Bizdēna Ē., et al. 1, 2, 3-Triazoles as leaving groups in purine chemistry: a three-step synthesis of N6-substituted-2-triazolyl-adenine nucleosides and photophysical properties thereof //Tetrahedron Letters. 2013. Vol. 54, N8. P. 850–853. https://doi.org/10.1016/j.tetlet.2012.11.095
  12. Meisenheimer K. M., Koch T. H. Photocross-Linking of Nucleic Acids to Associated Proteins // Critical Reviews in Biochemistry and Molecular Biology. 1997. Vol. 32, N2. P. 101–140. https://doi.org/10.3109/10409239709108550
  13. Salihovic A., Ascham A., Taladriz-Sender A., et al. Gram-scale enzymatic synthesis of 2′-deoxyribonucleoside analogues using nucleoside transglycosylase-2 // Chem. Sci. 2024. Vol. 15. P. 15399–15407. https://doi.org/10.1039/D4SC04938As
  14. Konkina M.A., Drenichev M. S., Nasyrova D. I., et al. Studies on enzymatic transglycosylation catalyzed by bacterial Nucleoside deoxyribosyltransferase II and Nucleoside phosphorylase for the synthesis of pyrimidine 2′-Deoxyribonucleosides containing modified heterocyclic base // Sustain. Chem. and Pharm. 2023. Vol. 32. P. 101011. https://doi.org/10.1016/j.scp.2023.101011
  15. Frieden M., Aviñó A., Eritja R. Convenient Synthesis of 8-Amino-2′-deoxyadenosine // Nucleosides, Nucleotides & Nucleic Acids. 2003. Vol. 22, N2. P. 193–202. https://doi.org/10.1081/NCN-120019521
  16. Lakshman M. K., Singh M. K., Parrish D., et al. Azide– Tetrazole equilibrium of C-6 azidopurine nucleosides and their ligation reactions with alkynes // The Journal of organic chemistry. 2010. Vol. 75, N8. P. 2461–2473.
  17. Drenichev M.S., Alexeev C. S., Kurochkin N. N., et al. Use of nucleoside phosphorylases for the preparation of purine and pyrimidine 2′-deoxynucleosides. // Adv. Synth. Catal. 2018. Vol.360. P. 305–312. https://doi.org/10.1002/adsc.201701005.
  18. Rabuffetti M., Bavaro, T., Semproli, R., et al. Synthesis of ribavirin, tecadenoson, and cladribine by enzymatic transglycosylation. // Catalysts. 2019. Vol. 9. P. 355. doi: 10.3390/catal9040355.
  19. Komodziński K., Nowak J., Lepczyńska J., et. al. Photochemistry of 6-azidopurine ribonucleoside in aqueous solution // Tetrahedron Lett. 2012. Vol. 53, N18. P. 2316–2318. https://doi.org/10.1016/j.tetlet.2012.02.103.

Supplementary files

Supplementary Files
Action
1. JATS XML
Download

Copyright (c) 2025 Russian Academy of Sciences