Journal article
Tissue targeting of multivalent GalNAc Le(x) terminated N-glycans in mice
Glycobiology (Oxford), Vol.10(12), pp.1341-1345
12/2000
DOI: 10.1093/glycob/10.12.1341
PMID: 11159926
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.
Details
- Title: Subtitle
- Tissue targeting of multivalent GalNAc Le(x) terminated N-glycans in mice
- Creators
- Yongsheng Yang - College of Pharmacy, University of Michigan, 428 Church Street, Ann Arbor, MI 48109-1065, USAV Hayden ThomasShouchin ManKevin G Rice
- Resource Type
- Journal article
- Publication Details
- Glycobiology (Oxford), Vol.10(12), pp.1341-1345
- DOI
- 10.1093/glycob/10.12.1341
- PMID
- 11159926
- NLM abbreviation
- Glycobiology
- ISSN
- 0959-6658
- eISSN
- 1460-2423
- Publisher
- England
- Grant note
- AI33189 / NIAID NIH HHS GM48049 / NIGMS NIH HHS
- Language
- English
- Date published
- 12/2000
- Academic Unit
- Pharmaceutical Sciences and Experimental Therapeutics; Craniofacial Anomalies Research Center; Medicinal and Natural Products Chemistry
- Record Identifier
- 9984065698102771
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