Versatile synthesis of bi- 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 coupling 1-thio-beta-D-galactose derivatives to the alpha- and epsilon-amino groups of L-lysine and L-lysyl-L-lysine via highly flexible hydrophilic 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 clustering effect known to occur with more complex oligomeric structures, i.e. tri- > bi-antennary; ii) dependent on the intergalactose distances (optimal interactions were observed for the tri-antennary structures with distances > 2 nm). These ligands, that can be easily conjugated to bioactive (macro) molecule carrier systems, could be useful for their targeting to hepatocytes.
D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D005690:Galactose / Q000031:analogs & derivatives* / Q000138:chemical synthesis; D006801:Humans; D008024:Ligands; D008113:Liver Neoplasms / Q000378:metabolism*; D015394:Molecular Structure; D051381:Rats; D011956:Receptors, Cell Surface / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D008024:Ligands; D011956:Receptors, Cell Surface; C039707:galactose receptor; D005690:Galactose