VERSATILE SYNTHESIS OF BI-ANTENNARY AND TRI-ANTENNARY GALACTOSE LIGANDS - INTERACTION WITH THE GAL GALNAC RECEPTOR OF HUMAN HEPATOMA-CELLS/

We have synthesized bi- and tri-antennary galactose ligands by couplin g 1-thio-beta-D-galactose derivatives to the alpha- and epsilon-amino groups of L-lysine and L-lysyl-L-lysine via highly flexible hydrophili c spacer arms that allow variation of their intergalactose distances. The interaction of these ligands with the Gal/GalNAc receptor of HepG2 cells showed a binding affinity that was: (i) in agreement with the c lustering effect known to occur with more complex oligomeric structure s, i.e. tri- > bi-antennary; ii) dependent on the intergalactose dista nces (optimal interactions were observed for the tri-antennary structu res with distances > 2 nm). These ligands, that can be easily conjugat ed to bioactive (macro) molecule carrier systems, could be useful for their targeting to hepatocytes.