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New ASGPR-targeted ligands based on glycoconjugated natural triterpenoids

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Abstract

New ligands for targeted delivery to the liver based on glycoconjugated natural triterpenoids are proposed. Simple chemical transformations of starting lupane triterpenes led to betulin or betulinic acid conjugates with N-acetyl-d-galactosamine linked through an isopropenyl fragment of the terpene skeleton. The obtained compounds were non-toxic in vitro to a series of cancer cell lines and normal cells. Molecular docking in silico and surface plasmon resonance spectroscopy revealed a high specificity of the synthesized glycotriterpenoids to the asialogly-coprotein receptor of hepatocytes.

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Authors and Affiliations

  1. Lomonosov Moscow State University, 1 Leninskie Gory, 119991, Moscow, Russian Federation

    E. Yu. Yamansarov, D. A. Skvortsov, A. V. Lopukhov, S. V. Kovalev, S. A. Evteev, R. A. Petrov, N. L. Klyachko, N. V. Zyk, E. K. Beloglazkina & A. G. Majouga

  2. Skolkovo Institute of Science and Technology, 100 ul. Novaya, 143025, Skolkovo, Russian Federation

    N. L. Klyachko

  3. Institute of Biochemistry and Genetics, Ufa Scientific Center of the Russian Academy of Sciences, 71 prosp. Oktyabrya, 450054, Ufa, Russian Federation

    Ya. A. Ivanenkov

  4. Moscow Institute of Physics and Technology (State University), 9 Instituskiiper., 141701, Dolgoprudnyi, Moscow region, Russian Federation

    Ya. A. Ivanenkov

  5. National University of Science and Technology MISiS, 4 Leninskiiprosp., 119049, Moscow, Russian Federation

    A. G. Majouga

  6. Dmitry Mendeleev University of Chemical Technology of Russia, 1 Build., 9 Miusskaya pl., 125047, Moscow, Russian Federation

    A. G. Majouga

Authors
  1. E. Yu. Yamansarov
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  2. D. A. Skvortsov
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  3. A. V. Lopukhov
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  4. S. V. Kovalev
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  7. N. L. Klyachko
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  8. N. V. Zyk
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  9. E. K. Beloglazkina
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  10. Ya. A. Ivanenkov
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Corresponding author

Correspondence to E. Yu. Yamansarov.

Additional information

The support from the Program for Development of M. V. Lomonosov Moscow State University is gratefully acknowledged: SPR spectral studies were performed on a Biacore X100 equipment purchased using financial support from the Program PNR 5–13. The authors are grateful to Thermo Fisher Scientific Inc. and MS Analitika (Moscow, Russia) and personally to Prof. A. A. Makarov for providing mass-spectrometric equipment used in the present work.

This work was financially supported by the Russian Science Foundation (Project No. 17-74-10204 (synthesis and cytotoxicity study) and Project No. 17-74-30012 (in silico molecular docking)) and the Skolkovo Institute of Science and Technology (Agreement SkolTech 182-MRA (estimation of affinity by SPR spectroscopy)).

Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 12, pp. 2331–2338, December, 2019.

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Yamansarov, E.Y., Skvortsov, D.A., Lopukhov, A.V. et al. New ASGPR-targeted ligands based on glycoconjugated natural triterpenoids. Russ Chem Bull 68, 2331–2338 (2019). https://doi.org/10.1007/s11172-019-2707-9

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  • DOI: https://doi.org/10.1007/s11172-019-2707-9

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