title: Tissue targeting of multivalent GalNAc Le(x) terminated N-glycans in mice.
abstract: N-Linked biantennary and triantennary oligosaccharides containing multiple terminal GalNAc Le(x) (GalNAcss1-4[Fuc-alpha1-3]GlcNAc) determinants were radioiodinated and their pharmacokinetics, biodistribution, and hepatic cellular localization were determined in mice. Pharmacokinetic analysis revealed GalNAc Le(x) biantennary and triantennary oligosaccharides had a similar mean residence time and steady-state volume of distribution but differed in their total body clearance rate due a shorter alpha half-life for GalNAc Le(x) triantennary. Biodistribution and whole-body-autoradiography studies revealed that both GalNAc Le(x) terminated biantennary and triantennary oligosaccharides predominately targeted to the liver, which accumulated 72% and 79% of the dose 30 min after administration, respectively. Separation of mouse liver parenchymal from non-parenchymal cells demonstrated both N-glycans were almost exclusively (94%) taken up by the parenchymal cells. By comparison, GalNAc terminated biantennary and triantennary N-glycans accumulated in the liver with a targeting efficiency of 73% and 81%, respectively. It is concluded that GalNAc and GalNAc Le(x) terminated N-glycans are recognized in vivo with equivalent affinity by the murine hepatic asialoglycoprotein receptor.
authors.affiliation: College of Pharmacy, University of Michigan, 428 Church Street, Ann Arbor, MI 48109-1065, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Yang
authors.forename: V H
authors.initials: VH
authors.lastname: Thomas
authors.forename: S
authors.initials: S
authors.lastname: Man
authors.forename: K G
authors.initials: KG
authors.lastname: Rice
mesh_terms: D000116:Acetylgalactosamine / Q000737:chemistry*; D000818:Animals; D002240:Carbohydrate Sequence; D016256:Lewis X Antigen / Q000737:chemistry / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D011134:Polysaccharides / Q000737:chemistry*
chemical_list: D016256:Lewis X Antigen; D011134:Polysaccharides; D000116:Acetylgalactosamine