Ligands of the asialoglycoprotein receptor for targeted gene delivery, part 1: Synthesis of and binding studies with biotinylated cluster glycosides containing N-acetylgalactosamine.

摘要: In order to develop the non-viral Bioplex vector system for targeted delivery of genes hepatocytes, we have evaluated structure-function relationship a number synthetic ligands designed specific interaction with hepatic lectin ASGPr. Biotinylated ligand derivatives containing two, three or six beta-linked N-acetylgalactosamine (GalNAc) residues were synthesized, bound fluorescent-labeled streptavidin and tested binding uptake HepG2 cells using flow cytometry analysis (FACS). Uptake efficiency increased displayed GalNAc units per ligand, in receptor dependent manner. Thus, derivative displaying showed highest efficacy both terms internalizing amount material taken up each cell. However, this higher was shown be due not so much sugar units, but accessibility (longer spacer). Improving flexibility trimeric through use longer spacer markedly influenced efficiency, while increasing above only provided minor contribution overall affinity. We hereby report details chemical synthesis studies vitro.