| Institution: | 1. Lomonosov Moscow State University, Chemistry Dept, Leninskie Gory, Building 1/3, GSP-1, Moscow 119991, Russian Federation;2. Moscow Institute of Physics and Technology (State University), 9 Institutskiy Lane, Dolgoprudny City, Moscow Region 141700, Russian Federation;3. National University of Science and Technology MISiS, 9 Leninskiy pr, Moscow 119049, Russian Federation;4. Skolkovo Institute of Science and Technology, 100 Novaya St., 143025 Skolkovo, Russian Federation;5. Dmitry Mendeleev University of Chemical Technology of Russia, Miusskaya Sq. 9, Moscow 125047, Russian Federation;6. Lomonosov Moscow State University, A.N. Belozersky Institute of Physico-Chemical Biology, Leninskye Gory, House 1, Building 40, Moscow 119992, Russian Federation;g. Institute of Biochemistry and Genetics Ufa Science Centre Russian Academy of Sciences (IBG RAS), Prosp. Oktybrya 71, Ufa, Bashkortostan 450054, Russian Federation;h. Lomonosov Moscow State University, Faculty of Bioengineering and Bioinformatics, Moscow, Russia |
| Abstract: | Asialoglycoprotein receptor (ASGP-R) is a promising biological target for drug delivery into hepatoma cells. Nevertheless, there are only few examples of small-molecule conjugates of ASGP-R selective ligand equipped by a therapeutic agent for the treatment of hepatocellular carcinoma (HCC). In the present work, we describe a convenient and versatile synthetic approach to novel mono- and multivalent drug-conjugates containing N-acetyl-2-deoxy-2-aminogalactopyranose and anticancer drug – paclitaxel (PTX). Several molecules have demonstrated high affinity towards ASGP-R and good stability under physiological conditions, significant in vitro anticancer activity comparable to PTX, as well as good internalization via ASGP-R-mediated endocytosis. Therefore, the conjugates with the highest potency can be regarded as a promising therapeutic option against HCC. |
