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Synthesis and Affinity of Novel Triantennary Ligands for the Asialoglycoprotein Receptor

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Abstract

Novel triantennary N-acetylgalactosamine derivatives of tris(hydroxymethyl)aminomethane were synthesized and used to form complexes with the asialoglicoprotein receptor expressed on the hepatocellular surface. The equilibrium dissociation constants (KD) of the complexes of the asialoglicoprotein receptor with the synthesized compounds were measured by surface plasmon resonance spectroscopy. The KD values were in the subnanomolar range, being 6 orders of magnitude lower than the respective values for the complex of the receptor with the natural N-acetylgalactosamine ligand. The resulting data suggest that the synthesized ligands are promising agents for targeted delivery of various therapeutic agents in hepatocytes.

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ACKNOWLEDGMENTS

The authors are grateful to the staff members of the Laboratory of Physicochemical Methods of Analysis of the Structure of Matter, Department of Chemistry, Lomonosov Moscow State University, Doctor of Chemical Sciences, Professor Al’bert Tarasovich Lebedev, Candidate of Chemical Sciences Sergei Vasil’evich Kovalev, and Andrei Alexandrovich Beloglazkin for help in the study.

Funding

The study was financially supported by the Russian Science Foundation through grant no. 21-73-00106 (Synthesis of Polyvalent Ligands of the Asialoglycoprotein Receptor) and grant no. 20-63-46029 (Affinity Study by Surface Plasmon ResonanceS), as well as the Development Program of the Moscow State University.

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  1. Lomonosov Moscow State University, Chemistry Department, 119991, Moscow, Russia

    R. A. Petrov, S. A. Petrov, D. A. Grishin, I. G. Kolmakov, D. S. Abramchuk, V. T. Tkachenko, E. A. Vlasova, S. Yu. Maklakova, A. V. Lopukhov, N. L. Klyachko & E. K. Beloglazkina

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  1. R. A. Petrov
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Correspondence to R. A. Petrov.

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Translated from Zhurnal Organicheskoi Khimii, 2023, Vol. 59, No. 2, pp. 165–179 https://doi.org/10.31857/S0514749223020027.

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Petrov, R.A., Petrov, S.A., Grishin, D.A. et al. Synthesis and Affinity of Novel Triantennary Ligands for the Asialoglycoprotein Receptor. Russ J Org Chem 59, 224–236 (2023). https://doi.org/10.1134/S1070428023020021

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