title: Design, synthesis and evaluation of monovalent ligands for the asialoglycoprotein receptor (ASGP-R).
abstract: A series of novel aryl-substituted triazolyl D-galactosamine derivatives was synthesized as ligands for the carbohydrate recognition domain of the major subunit H1 (H1-CRD) of the human asialoglycoprotein receptor (ASGP-R). The compounds were biologically evaluated with a newly developed competitive binding assay, surface plasmon resonance and by a competitive NMR binding experiment. With compound 1b, a new ligand with a twofold improved affinity to the best so far known D-GalNAc was identified. This small, drug-like ligand can be used as targeting device for drug delivery to hepatocytes.
authors.affiliation: Institute of Molecular Pharmacy, Pharmacenter, University of Basel, Klingelbergstrasse 50, CH-4056 Basel, Switzerland.
authors.forename: Daniela
authors.initials: D
authors.lastname: Stokmaier
authors.forename: Oleg
authors.initials: O
authors.lastname: Khorev
authors.forename: Brian
authors.initials: B
authors.lastname: Cutting
authors.forename: Rita
authors.initials: R
authors.lastname: Born
authors.forename: Daniel
authors.initials: D
authors.lastname: Ricklin
authors.forename: Thomas O G
authors.initials: TO
authors.lastname: Ernst
authors.forename: Fabienne
authors.initials: F
authors.lastname: Böni
authors.forename: Kathrin
authors.initials: K
authors.lastname: Schwingruber
authors.forename: Martin
authors.initials: M
authors.lastname: Gentner
authors.forename: Matthias
authors.initials: M
authors.lastname: Wittwer
authors.forename: Morena
authors.initials: M
authors.lastname: Spreafico
authors.forename: Angelo
authors.initials: A
authors.lastname: Vedani
authors.forename: Said
authors.initials: S
authors.lastname: Rabbani
authors.forename: Oliver
authors.initials: O
authors.lastname: Schwardt
authors.forename: Beat
authors.initials: B
authors.lastname: Ernst
mesh_terms: D037263:Asialoglycoprotein Receptor / Q000737:chemistry / Q000378:metabolism*; D001667:Binding, Competitive; D015195:Drug Design; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D020349:Surface Plasmon Resonance
chemical_list: D037263:Asialoglycoprotein Receptor; D008024:Ligands