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Glycobiology, 2000, Vol. 10, No. 12 1341-1345
© 2000 Oxford University Press

Tissue targeting of multivalent GalNAc Lex terminated N-glycans in mice

Yongsheng Yang, V.Hayden Thomas, Shouchin Man and Kevin G. Rice1

College of Pharmacy, University of Michigan, 428 Church Street, Ann Arbor, MI 48109–1065, USA

N-Linked biantennary and triantennary oligosaccharides containing multiple terminal GalNAc Lex (GalNAcß1–4[Fuc-{alpha}1–3]GlcNAc) determinants were radioiodinated and their pharmacokinetics, biodistribution, and hepatic cellular localization were determined in mice. Pharmacokinetic analysis revealed GalNAc Lex 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 Lex triantennary. Biodistribution and whole-body-autoradiography studies revealed that both GalNAc Lex 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 Lex terminated N-glycans are recognized in vivo with equivalent affinity by the murine hepatic asialoglycoprotein receptor.

1 To whom correspondence should be addressed


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