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...

Full description

Saved in:
Bibliographic Details
Published in:Bioorganic & medicinal chemistry 2009-10, Vol.17 (20), p.7254-7264
Main Authors: Stokmaier, Daniela, Khorev, Oleg, Cutting, Brian, Born, Rita, Ricklin, Daniel, Ernst, Thomas O.G., Böni, Fabienne, Schwingruber, Kathrin, Gentner, Martin, Wittwer, Matthias, Spreafico, Morena, Vedani, Angelo, Rabbani, Said, Schwardt, Oliver, Ernst, Beat
Format: Article
Language:English
Subjects:
Asialoglycoprotein receptor (ASGP-R)
Asialoglycoprotein Receptor - chemistry
Asialoglycoprotein Receptor - metabolism
Binding, Competitive
Biological and medical sciences
Competitive binding assay
Competitive NMR binding experiments
Drug Design
Electrophoresis, Polyacrylamide Gel
Humans
Ligands
Magnetic Resonance Spectroscopy
Medical sciences
Miscellaneous
Models, Molecular
Pharmacology. Drug treatments
Surface Plasmon Resonance
Triazolyl d-galactosamine derivatives
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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-Gal NAc was identified. This small, drug-like ligand can be used as targeting device for drug delivery to hepatocytes.
ISSN:0968-0896
1464-3391
DOI:10.1016/j.bmc.2009.08.049