Synthesis and affinity of novel asialoglycoprotein receptor triantennary ligands

New triantennary N -acetylgalactosamine derivatives of tris(hydroxymethyl)aminomethane were synthesized and used to form complexes with asialoglicoprotein receptor, originally found on hepatocytes. Equilibrium dissociation constants ( K D) of asialoglicoprotein receptor and obtained compounds were measured using surface plasmon resonance spectroscopy technique. The K D values were in the subnanomolar range, being 6 orders of magnitude lower than the K D of the complex of the receptor and N -acetylgalactosamine, its native ligand. The synthesized ligands exhibit much stronger binding to receptor in comparison to the natural ligand. These results suggest that synthesized ligands are promising agents for the targeted delivery of various therapeutic agents in hepatocytes.