Synthesis of Multivalent Galactosides as Targeting Ligand for Gene Delivery

Abstract

A series of novel bifunctional glycolipid ligands designed to bind with high affinity and specificity to the asialoglycoprotein receptor (ASGP-R) has been synthesized and assayed in vitro on human hepatoma cells, HepG2, derived from parenchymal liver cells. The compounds bear five β-linked Gal moieties linked to the core scaffold, hexa-antennary alcohol, for interaction with the binding site of the ASGP-R. The liposome/DNA complexes containing the glycolipid ligands are efficiently recognized by ASGP-R and exhibited high affinity and transfection activity.

Keywords:

• Gene delivery
• hepatocyte targeting
• multivalent galactosides
• synthesis

ACKNOWLEDGMENTS

This work was supported by the National Natural Science Foundation of China (No. 30672537) and Ministry of Education of China (No. 20050610085).