Your browser doesn't support javascript.
loading
Synthesis and Evaluation of New Trivalent Ligands for Hepatocyte Targeting via the Asialoglycoprotein Receptor.
Reshitko, Galina S; Yamansarov, Emil Yu; Evteev, Sergei A; Lopatukhina, Elena V; Shkil', Dmitry O; Saltykova, Irina V; Lopukhov, Anton V; Kovalev, Sergey V; Lobov, Alexander N; Kislyakov, Ivan V; Burenina, Olga Yu; Klyachko, Natalia L; Garanina, Anastasiia S; Dontsova, Olga A; Ivanenkov, Yan A; Erofeev, Alexander S; Gorelkin, Peter V; Beloglazkina, Elena K; Majouga, Alexander G.
Affiliation
  • Reshitko GS; Chemistry Department, Lomonosov Moscow State University, Moscow, 119991, Russian Federation.
  • Yamansarov EY; Chemistry Department, Lomonosov Moscow State University, Moscow, 119991, Russian Federation.
  • Evteev SA; National University of Science and Technology MISiS, Moscow, 119049, Russian Federation.
  • Lopatukhina EV; Chemistry Department, Lomonosov Moscow State University, Moscow, 119991, Russian Federation.
  • Shkil' DO; Chemistry Department, Lomonosov Moscow State University, Moscow, 119991, Russian Federation.
  • Saltykova IV; Chemistry Department, Lomonosov Moscow State University, Moscow, 119991, Russian Federation.
  • Lopukhov AV; Chemistry Department, Lomonosov Moscow State University, Moscow, 119991, Russian Federation.
  • Kovalev SV; Chemistry Department, Lomonosov Moscow State University, Moscow, 119991, Russian Federation.
  • Lobov AN; Chemistry Department, Lomonosov Moscow State University, Moscow, 119991, Russian Federation.
  • Kislyakov IV; Ufa Institute of Chemistry of the Ufa Federal Research Centre of the Russian Academy of Sciences, Ufa, 450054, Russian Federation.
  • Burenina OY; Chemistry Department, Lomonosov Moscow State University, Moscow, 119991, Russian Federation.
  • Klyachko NL; Skolkovo Institute of Science and Technology, Skolkovo, 143026, Russian Federation.
  • Garanina AS; Chemistry Department, Lomonosov Moscow State University, Moscow, 119991, Russian Federation.
  • Dontsova OA; Skolkovo Institute of Science and Technology, Skolkovo, 143026, Russian Federation.
  • Ivanenkov YA; National University of Science and Technology MISiS, Moscow, 119049, Russian Federation.
  • Erofeev AS; Chemistry Department, Lomonosov Moscow State University, Moscow, 119991, Russian Federation.
  • Gorelkin PV; Skolkovo Institute of Science and Technology, Skolkovo, 143026, Russian Federation.
  • Beloglazkina EK; Moscow Institute of Physics and Technology (State University), Dolgoprudny City, Moscow Region 141700, Russian Federation.
  • Majouga AG; Institute of Biochemistry and Genetics, Russian Academy of Science (IBG RAS) of the Ufa Federal Research Centre, Ufa, 450054, Russian Federation.
Bioconjug Chem ; 31(5): 1313-1319, 2020 05 20.
Article in En | MEDLINE | ID: mdl-32379426
Since the asialoglycoprotein receptor (also known as the "Ashwell-Morell receptor" or ASGPR) was discovered as the first cellular mammalian lectin, numerous drug delivery systems have been developed and several gene delivery systems associated with multivalent ligands for liver disease targeting are undergoing clinical trials. The success of these systems has facilitated the further study of new ligands with comparable or higher affinity and less synthetic complexity. Herein, we designed two novel trivalent ligands based on the esterification of tris(hydroxymethyl) aminomethane (TRIS) followed by the azide-alkyne Huisgen cycloaddition with azido N-acetyl-d-galactosamine. The presented triazolyl glycoconjugates exhibited good binding to ASGPR, which was predicted using in silico molecular docking and assessed by a surface plasmon resonance (SPR) technique. Moreover, we demonstrated the low level of in vitro cytotoxicity, as well as the optimal spatial geometry and the required amphiphilic balance, for new, easily accessible ligands. The conjugate of a new ligand with Cy5 dye exhibited selective penetration into HepG2 cells in contrast to the ASGPR-negative PC3 cell line.
Subject(s)

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Hepatocytes / Asialoglycoprotein Receptor Type of study: Prognostic_studies Limits: Humans Language: En Journal: Bioconjug Chem Journal subject: BIOQUIMICA Year: 2020 Document type: Article Country of publication:

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Hepatocytes / Asialoglycoprotein Receptor Type of study: Prognostic_studies Limits: Humans Language: En Journal: Bioconjug Chem Journal subject: BIOQUIMICA Year: 2020 Document type: Article Country of publication: