Synthesis of cluster galactosides with high affinity for the hepatic asialoglycoprotein receptor.

High-affinity ligands for the asialoglycoprotein receptor, which is uniquely localized on the parenchymal liver cell and recognizes oligoantennary galactosides, might be utilized as homing device to specifically target drugs or genes to parenchymal liver cells. In the present study, the synthesis of galactose-terminated triantennary glycosides, provided with various spacers between the beta-galactopyranosyl moieties and the branching point of the dendrite, is described. N-[Tris[[(methylthio)methoxy]methyl]methyl]-N alpha-[1-(6- methyladipy)]glycinamide (3b) was glycosylated with monogalactosyl derivatives, containing propanediol or ethylene glycol units as hydrophilic spacer moieties, to yield the corresponding cluster galactosides.

Specific targeting of the antiviral drug 5-iodo 2'-deoxyuridine to the parenchymal liver cell using lactosylated poly-L-lysine.

In this study, we describe the development and characterization of lactosylated poly-L-lysine as a potential carrier for targeting anti-viral drugs to the parenchymal liver cell. Poly-L-lysine (M(r) 38,000) was modified with 2 to 130 lactose residues per molecule poly-L-lysine. In vitro competition studies for the asialoglycoprotein receptor on parenchymal liver cells using 125I-asialoorosomucoid as radioligand revealed that mild modification of poly-L-lysine with only five lactose residues was sufficient for high affinity competition.

Ligand size is a major determinant of high-affinity binding of fucose- and galactose-exposing (lipo)proteins by the hepatic fucose receptor.

Previous in vivo studies have demonstrated that small galactose-exposing particles are preferentially internalized by the asialoglycoprotein receptor on the parenchymal liver cell and large particles by the galactose-particle receptor on the Kupffer cell. In this study, we have investigated using in vitro binding studies whether the affinity for either receptor is affected by the ligand size. The asialoglycoprotein receptor appeared to bind and process lactosylated proteins irrespective of their size.