Design, synthesis and evaluation of monovalent ligands for the asialoglycoprotein receptor (ASGP-R).
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.
Stokmaier
Daniela
D
Institute of Molecular Pharmacy, Pharmacenter, University of Basel, Klingelbergstrasse 50, CH-4056 Basel, Switzerland.
Khorev
Oleg
O
Cutting
Brian
B
Born
Rita
R
Ricklin
Daniel
D
Ernst
Thomas O G
TO
Böni
Fabienne
F
Schwingruber
Kathrin
K
Gentner
Martin
M
Wittwer
Matthias
M
Spreafico
Morena
M
Vedani
Angelo
A
Rabbani
Said
S
Schwardt
Oliver
O
Ernst
Beat
B
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
D037263:Asialoglycoprotein Receptor; D008024:Ligands