Design, synthesis and evaluation of monovalent ligands for the asialoglycoprotein receptor (ASGP-R)

Bioorg Med Chem. 2009 Oct 15;17(20):7254-64. doi: 10.1016/j.bmc.2009.08.049. Epub 2009 Aug 29.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Asialoglycoprotein Receptor / chemistry
  • Asialoglycoprotein Receptor / metabolism*
  • Binding, Competitive
  • Drug Design*
  • Electrophoresis, Polyacrylamide Gel
  • Humans
  • Ligands
  • Magnetic Resonance Spectroscopy
  • Models, Molecular
  • Surface Plasmon Resonance

Substances

  • Asialoglycoprotein Receptor
  • Ligands