title: New and more efficient multivalent glyco-ligands for asialoglycoprotein receptor of mammalian hepatocytes.
abstract: New multi-valent, carbohydrate ligands that contain terminal N-acetylgalactosamine (GalNAc) or lactose (Lac) were prepared using a nitrilotriacetic acid (NTA) derivative of L-lysine as scaffold. Tri-valent structures were prepared by attaching an ω-amino glycoside of GalNAc or Lac to each of the three carboxyl groups of N(ε)-protected N(α)-dicarboxymethyl-L-lysine. In addition, a hexa-valent lactoside was synthesized by attaching N(ε)-deprotected trivalent lactoside to each of the carboxyl group of N(α)-(trifluoroacetamido)hexanoyl L-aspartic acid. Tri-valent GalNAc glycosides and the hexa-valent lactoside had high affinity (dissociation constants approaching nM) for rat hepatocytes. The hexa-valent lactoside, after de-N(ε)-protection, was modified with a chelator, diethylenetriaminepentaacetic acid (DTPA), through which a fluorescent or radioactive tag, such as europium or indium, can be firmly attached. Intravenous infusion of (111)Indium-tagged hexa-valent lactoside to rats and mice resulted in nearly exclusive accumulation of radioactivity in the liver.
authors: Department of Biology, Johns Hopkins University, Baltimore, MD 21218, USA.
authors: Reiko T
authors: RT
authors: Lee
authors: Mei-Hui
authors: MH
authors: Wang
authors: Wuu-Jyh
authors: WJ
authors: Lin
authors: Yuan C
authors: YC
authors: Lee
mesh_terms: D000116:Acetylgalactosamine; D000818:Animals; D037263:Asialoglycoprotein Receptor / Q000378:metabolism*; D002478:Cells, Cultured; D006027:Glycosides / Q000008:administration & dosage / Q000378:metabolism* / Q000494:pharmacology; D022781:Hepatocytes / Q000737:chemistry* / Q000166:cytology / Q000187:drug effects; D007785:Lactose; D008024:Ligands; D008099:Liver / Q000378:metabolism; D051379:Mice; D011485:Protein Binding; D051381:Rats
chemical_list: D037263:Asialoglycoprotein Receptor; D006027:Glycosides; D008024:Ligands; C008245:lactosides; D007785:Lactose; D000116:Acetylgalactosamine